1. Follow Best Accounting practices

Once you have reached the post-award phase, adhering to fund accounting best practices is essential. Tracking and managing expenses in compliance with grant guidelines ensures the effectiveness and transparency of the project, which is crucial for future grant applications. It would be best to allocate direct and indirect expenses based on the approved budget. However, tracking program expenses and activities according to grant requirements may require significant time and effort.

2. Understand The Reporting requirements

NIH requires recipients to submit progress and financial reports periodically. Progress reports should be submitted via the Research Performance Progress Report (RPPR) module. There are three types of RPPRs: annual, interim, and final. It is important to adhere to the deadlines specified by NIH for these reports.

These reports can be submitted through the eRA Commons. They should encompass achievements pertaining to annual goals, upcoming project plans, documentation of manuscripts and publications produced by project contributors, modifications to the project’s key personnel, current or projected project hurdles or delays, strategies for overcoming these challenges, noteworthy alterations concerning human or animal subject involvement, enrollment reports for clinical studies, and other relevant information.

3. Adhere to NIH policies and regulations:

NIH has various policies and regulations that govern the use of grants. These policies safeguard the credibility of research outcomes and maintain transparency, accountability, and adherence to ethical standards. Ensure that your research project aligns with NIH policies and regulations. Review updates on NIH policies, guidelines, and any changes concerning grant management continually.

4. Hire The Right Staff

Apart from managing finances and adhering to reporting guidelines and NIH policies, having the right staff with the appropriate skills and expertise is also important. Identify workforce utilization plans and ensure that your staff’s workload aligns with grant objectives. Many businesses have natural ebbs and flows, and finding the right balance may be challenging. Temporary staffing is an option for supplementing your staff during peak periods, such as research cycles or clinical trials, where additional resources may be necessary. A staffing agency that provides scientific and technical candidates for federal agencies can be a valuable resource when you need to hire quickly. Firms experienced in screening, interviewing, and managing contractor relationships can save your organization time and money.

5. Closing Out Grant

When the grant period comes to an end, and if a subsequent competing segment is not funded, or if the grant is transferred from one institution to another, the NIH requires the submission of a Final Invention Statement and Certification (HHS 568) within 120 days. In cases where the grant is ending, the Final Invention Statement and Certification, along with other closeout documents, can be submitted directly to the relevant NIH institute or center.

Conclusion:

Effectively using a federal NIH Grant Award requires diligent efforts, understanding, and adherence to the post-award phase. Understanding the grant award budget, reporting requirements, adhering to NIH policies and regulations, working with your grant officer, and planning for the closeout phase are critical steps to ensure the optimal utilization of the grant award. By following these steps, grant awardees can maximize the positive impact of the project, advance research fields, and maintain transparency and accountability.

Disclaimer:

The purpose of this information is solely to provide general knowledge and should not be construed as legal advice. Consult with your legal counsel to ensure your specific workplace drug testing policies comply with the most current laws and regulations.

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Structure of NIH

The NIH is a federal agency under the  United States Department of Health and Human Services. It comprises 27 different Institutes and Centers (ICs), each focusing on a specific area of medical research, such as cancer, heart disease, or infectious diseases. These institutes and centers are collectively called ICs, providing funding opportunities for researchers whose work aligns with their specific mission.

What NIH Looks For

NIH aims to fund research to contribute to knowledge advancements and scientific breakthroughs. They seek research projects that align with their mission to improve human health and promote scientific discovery.

One of the first things to understand about the NIH is that many different types of grant programs are available, each with its own set of eligibility requirements. 80% of the NIH budget supports investigators in over 2,500 universities, medical schools, and other research organizations worldwide. To determine which IC may be interested in your research, the NIH has an easy-to-use Matchmaker tool in RePORTER, which helps find an NIH program official responsible for that area of research.

Who is eligible

To be eligible for NIH grants, organizations and individuals must meet certain criteria based on the specific grant program they are applying for. It is important to note that while the principal investigator typically writes and conceives the application, the applicant institution is recognized as the recipient for most grant types. Eligibility information for each funding opportunity can typically be found in Section III of the grant’s documentation.

Types of Grant Programs

NIH offers a wide variety of grant programs to support research across a range of scientific fields. Some of the most commonly used grant programs include:

• Research Grants (R-series): These grants support a wide range of scientific research projects, including basic, translational, and clinical research.
• Career Development Awards (K-series): These grants support the career development of investigators at different stages of their career.
• Research Training and Fellowship Awards (T32, F31, F32): These grants support the training of researchers at different stages of their careers.
• Center Grants (P-series): These grants support the establishment of research centers that focus on particular scientific fields.
• Resource Grants (various series): provides access to resource and research related support.
• Trans-NIH Programs: supports broad programs that are trans-NIH.

Types of Grant Applications

When submitting a grant application to the NIH, it is important to understand the different types of available applications.

These include:

• New applications: first time submissions.
• Renewal applications: ongoing projects that need additional funding.
• Revision applications: used to change the scope or direction of a project.
• Resubmission applications: for projects that were previously rejected.

Insight: Each type of application has its specific requirements, such as deadlines and submission formats, so it is crucial to carefully review the documentation for each grant program to determine the appropriate application type.

Other Key Factors NIH Looks For

In addition to these basic requirements, the NIH looks for a few key factors when considering grant proposals. NIH prioritizes proposals that are of high scientific caliber and significantly advance the field of study in question. Other factors that may be considered include the feasibility of the proposed research and the quality of the principal investigator’s track record in conducting similar research.

Conclusion

Understanding the structure and approach of the NIH is essential for anyone interested in pursuing grant funding for medical research. By learning about the various grant programs, eligibility requirements, and types of grant applications, researchers and organizations can best position themselves to receive funding from this critical organization.

About Astrix

Astrix has been providing services to branches of the federal government, along with various municipal and state governments, in the United States for over two decades.

We are a company of scientists with technical training and specific expertise and hands-on experience in life science environments. We utilize our Strategic Consulting, Application & Platform Services, and Scientific & IT Staffing teams to consistently provide high-value staffing, scientific and technical solutions to analytical laboratory programs within United States governmental agencies.

Contact us to learn more about how we can support your organization.

Resources

• How to apply guide
• Types of applications
• Grant Process Information

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Recent National Institutes of Health Research

NIH study finds loss of ‘youth’ protein may drive aging in the eye

According to new research in mice from the National Eye Institute (NEI), the protein pigment epithelium-derived factor (PEDF), which safeguards retinal support cells, may be lost due to aging and lead to age-related changes in the eye.

“People have called PEDF the ‘youth’ protein because it is abundant in young retinas, but it declines during aging,” said Patricia Becerra, Ph.D., chief of NEI’s Section of Protein Structure and Function and senior author of the study. “This study showed for the first time that just removing PEDF leads to a host of gene changes that mimic aging in the retina.”

Past research from Becerra’s lab and others has shown that PEDF protects retinal cells from damage and abnormal blood vessel growth, thanks to its ability to promote the differentiation of retinal precursor cells. When PEDF binds to its receptor, PEDF-R, it activates it to break down lipid molecules (a crucial component of the outer segment recycling process). PEDF also directly inhibits VEGF (vascular endothelial growth factor), a protein that promotes abnormal blood vessel growth.

To investigate the retinal function of PEDF, Becerra and colleagues studied a mouse model lacking the PEDF gene (Serpin1). The retinas of these PEDF-negative mice appeared normal at first, but when the cellular structure of the retina was examined, it showed that RPE cell nucleus sizes had increased. RPE cells also activated four genes linked to again and cellular senescence, showed significantly low PEDF receptor levels, and accumulated unprocessed lipids and other photoreceptor outer segment components in the RPE layer of the retina.

*”One of the most striking things was this reduction in the PEDF receptor on the surface of the RPE cells in the mouse lacking the PEDF protein,” said the study’s lead author, Ivan Rebustini, Ph.D., a staff scientist in Becerra’s lab. “It seems there’s some sort of feedback-loop involving PEDF that maintains the levels of PEDF-R and lipid metabolism in the RPE.”

The study was made possible by the NEI intramural program. The federal government’s research on the visual system and eye diseases is led by the National Eye Institute (NEI). For more information about NIH and its programs, visit www.nih.gov.

National Institutes of Health launches clinical trial of mRNA Nipah virus vaccine

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, has launched an early-stage clinical study evaluating a vaccine to prevent Nipah virus infection.

Nipah virus is a zoonotic pathogen that can cause severe respiratory and neurological diseases in humans. The virus is found in several Southeast Asian countries, including Bangladesh, India, and Malaysia. No specific treatment or vaccine is available for Nipah virus infection, which has a high fatality rate.

“Nipah virus poses a considerable pandemic threat because it mutates relatively easily, causes disease in a wide range of mammals, can transmit from person to person, and kills a large percentage of the people it infects,” said NIAID Director Anthony S. Fauci, M.D. “The need for a preventive Nipah virus vaccine is significant.”

The experimental vaccine is based on the same mRNA technology used for the COVID-19 vaccine and was created by Moderna, Inc and the NAID Vaccine Research Center. The novel mRNA-1215 Nipah virus vaccine will be studied in a dose-escalation clinical trial to assess its safety, tolerability, and immune response-generating capacity in 40 adults 18 to 60.

For more information about the clinical trial, visit ClinicalTrials.gov using the study identifier NCT05398796.

The NIAID funds and supports research at NIH throughout the United States and worldwide to investigate the causes of infectious and immunological diseases and develop more effective ways to prevent, detect, and treat these illnesses. The NIAID website provides news releases, fact sheets, and other NIAID-related materials.

Dabrafenib–Trametinib Combination Approved for Solid Tumors with BRAF Mutations

The Food and Drug Administration (FDA) has approved the combined treatment of dabrafenib (Tafinlar) and trametinib (Mekinist) for patients with nearly any sort of advanced solid tumor that contains a specific mutation in the gene BRAF. Dabrafenib and trametinib block different growth-promoting signals in tumor cells activated by the V600E BRAF mutation.

The FDA’s decision was based on data from three clinical trials, including two with adult patients and one with children. Some participants in the study had rare tumors, such as biliary tract cancer, ovarian cancer, and glioma (a type of brain tumor).

“Many types of metastatic cancers are tested for BRAF mutations, and the FDA approval is one more reason to have this testing,” said Lyndsay Harris, M.D. She leads NCI’s Cancer Diagnosis Program. She is also a lead investigator with NCI-MATCH, one of the clinical trials that led to the new approval.

The clinical trials enrolled adult patients with different types of tumors and assigned them to baskets based on criteria such as the molecular features of their tumors. The Novartis pediatric trial included low-grade gliomas and Langerhans cell histiocytosis patients who had relapsed after initial therapy or resisted treatment.

Overall response rates were 46%, 33%, and 50% for adults with biliary tract cancer, high-grade gliomas, and low-grade gliomas, respectively. In children, the overall response rate was 25%. Most of these individuals had responses that persisted for at least six months, and 44 percent had responses that lasted longer than a year.

The most common side effects of the combination therapy in adults included fever, fatigue, nausea, and rash. “The treatment was well tolerated,” Dr. Harris said. “The side effects were identical to those reported in previous trials of the dabrafenib–trametinib combination.”

The adverse effects in pediatric participants were comparable to those in the adult trials.

Basket trials like these might help researchers overcome current clinical restrictions by allowing them to compare various therapies in a wide range of unconventional malignancies.

“As we learn more about the molecular underpinnings of cancer, [basket trials] will continue to become more common,” predicted Dr. Salama, director of the melanoma program at Duke Cancer Institute and co-lead of the NCI-MATCH sub-study. “These studies are complicated to conduct, but they may also be one of the best ways to bring new treatment options to the clinic.”

Preterm Birth More Likely With Exposure to Phthalates

According to a study by the National Institutes of Health (NIH), women with higher levels of phthalate metabolites in their urine were more likely to give birth preterm. Phthalates are used in personal care items, such as fragrances and cleansers, solvents, detergents, and food packaging.

“Having a preterm birth can be dangerous for both baby and mom, so it is important to identify risk factors that could prevent it,” According to Dr. Kelly Ferguson, an epidemiologist at the National Institute of Environmental Health Sciences (NIEHS) and the lead author of the study.

Ferguson and her team analyzed data from 16 studies of over 6 thousand pregnant women in the USA who delivered between 1983-2018. The study found that higher levels of many phthalate metabolites were linked to a higher risk of preterm delivery. 9% or 539 of the women in the study delivered preterm, and Phthalate metabolites were detected in over 96% of urine samples.

Interventions that target behaviors, such as attempting to purchase phthalate-free personal care goods (if mentioned on the label), corporate initiatives to decrease phthalates in their goods, or adjustments in standards and regulations, can help reduce exposure and safeguard pregnancies.

“It is difficult for people to completely eliminate exposure to these chemicals in everyday life, but our results show that even small reductions within a large population could have positive impacts on both mothers and their children,” said Barrett Welch, Ph.D., a postdoctoral fellow at NIEHS and first author on the study.

Additional research is needed to understand how phthalates might harm pregnancy and if there are any methods for moms to reduce their exposures.

Researchers discover how sound reduces pain in mice

A new study of how sound reduces pain in mice may point to more effective pain therapies. The study was led by researchers at the National Institute of Dental and Craniofacial Research (NIDCR), the University of Science and Technology of China, Hefei; and Anhui Medical University, Hefei, China.

“We need more effective methods of managing acute and chronic pain, and that starts with gaining a better understanding of the basic neural processes that regulate pain,” said NIDCR Director Rena D’Souza, D.D.S., Ph.D. “By uncovering the circuitry that mediates the pain-reducing effects of sound in mice, this study adds critical knowledge that could ultimately inform new approaches for pain therapy.”

The researchers exposed mice with inflamed paws to three types of sound: pleasant music, an unpleasant rearrangement of the same piece, and white noise. When all three sounds were played at a low level relative to background noise, their ability to reduce pain sensitivity was comparable. Higher volumes of the same noises did not affect pain perceptivity.

“We were really surprised that the intensity of sound, and not the category or perceived pleasantness of sound, would matter,” said co-senior author Yuanyuan (Kevin) Liu, Ph.D., a Stadtman tenure-track investigator at NIDCR.

Researchers used non-infectious viruses and bright colors to map connections between regions to understand how this impact works in the brain. They located a pathway from the auditory cortex. In the absence of sound, light- and small molecule-based techniques that suppressed the pathway reproduced the pain-killing effects of low-intensity noise while turning it on restored sensitivity to pain.

The findings may be a starting point for future research to determine whether animal data apply to humans and, if they do, whether they are linked with other health concerns.

Small NIH study reveals how immune response triggered by COVID-19 may damage the brain

A new study by researchers from the National Institute of Neurological Disorders and Stroke (NINDS) shows that COVID-19 infection causes an immune response in the brain’s blood vessels, resulting in short- and long-term neurological issues.

“Patients often develop neurological complications with COVID-19, but the underlying pathophysiological process is not well understood,” said Avindra Nath, M.D., clinical director at NINDS and the senior author of the study. “We had previously shown blood vessel damage and inflammation in patients’ brains at autopsy, but we didn’t understand the cause of the damage. I think in this paper we’ve gained important insight into the cascade of events.”

When studying the brain of nine individuals who died from the virus, Dr. Nath and his team discovered immune complexes on the cell surface, demonstrating that COVID-19 antibodies may mistakenly target blood-brain barrier cells (made up of tightly packed endothelial cells). The findings suggest that the immune system is involved in an antibody-driven assault that activates endothelial cells.

“Activation of the endothelial cells brings platelets that stick to the blood vessel walls, causing clots and leakage to occur. At the same time the tight junctions between the endothelial cells get disrupted causing them to leak,” Dr. Nath explained. “Once leakage occurs, immune cells such as macrophages may come to repair the damage, setting up inflammation. This, in turn, causes damage to neurons.”

In regions with endothelial cell damage, researchers discovered that 300 genes linked to oxidative stress, DNA damage, and metabolic dysregulation were downregulated, while six others were upregulated. It’s possible that antibodies against the SARS-CoV-2 spike protein could bind to the ACE2 receptor, which the virus uses to enter cells. However, it remains unclear what antigen the immune response targets as the virus was not detected in the brains of the individuals they studied.

“It is quite possible that this same immune response persists in Long COVID patients resulting in neuronal injury,” said Dr. Nath. “There could be a small, indolent immune response that is continuing, which means that immune-modulating therapies might help these patients. So these findings have very important therapeutic implications.”

Understanding how COVID-19 SARS-CoV-2 infection might cause brain damage may aid the development of treatments for COVID-19 patients who suffer from long-term neurological disorders.

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Accelerating Precision Environmental Health: Demonstrating the Value of the Exposome

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Complex Exposures in Breast Cancer: Unraveling the Role of Environmental Mixtures

Wednesday, August 24 – Thursday, August 25, 2022

NIH Hosting Two-Part Webinar on Implementing the NIH Data Management and Sharing Policy

Thursday, August 11, 2022, from 1:30–3:00 p.m. (ET) and Thursday, September 22, 2022, from 1:30–3:00 p.m. (ET)

Irreducible Subjects: Disability and Genomics in the Past, Present and Future 

Thursday, October 6, 2022, 10:00 am to Friday, October 7, 2022, 5:00 pm (registration required)

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Recent NIH Research

NIH researchers discover new genetic eye disease

National Eye Institute (NEI) researchers discovered a new disease affecting the macula. NEI is part of the National Institutes of Health (NIH), a medical research agency that is a part of the U.S. Department of Health and Human Services.

Macular dystrophies are a group of degenerative diseases that cause progressive vision loss by damaging the macula, the small central area of the retina responsible for sharp, straight-ahead vision. These diseases are typically due to mutations in genes such as ABCA4, BEST1, PRPH2, and TIMP3.

Patients with Sorsby Fundus Dystrophy, a genetic eye disease characterized by TIMP3 variants, typically experience symptoms in adulthood. They frequently have rapid visual acuity fluctuations resulting from choroidal neovascularization– new, abnormal blood vessels that develop beneath the retina and leak fluid, causing vision impairment. The TIMP3 gene variants identified so far are all in the mature protein after cleaving from the RPE cells.

“We found it surprising that two patients had TIMP3 variants not in the mature protein but in the short signal sequence the gene uses to ‘cut’ the protein from the cells. We showed these variants prevent cleavage, causing the protein to be stuck in the cell, likely leading to retinal pigment epithelium toxicity,” said Bin Guan, Ph.D., lead author.

To confirm that the two new TIMP3 variants are linked to this unusual maculopathy, the research team conducted clinical investigations and genetic testing of family members.

“Discovering novel disease mechanisms, even in known genes like TIMP3, may help patients that have been looking for the correct diagnosis, and will hopefully lead to new therapies for them,” said Rob Hufnagel, M.D., Ph.D., senior author and director of the Ophthalmic Genomics Laboratory at NEI.

NEI Intramural Research Program supported this research. The National Eye Institute (NEI) is a medical research body in the United States government, part of the National Institutes of Health. The NEI is the federal government’s primary agency for studying the visual system and eye diseases. NEI funds basic and clinical science programs to create sight-saving medications and address the specific needs of individuals with vision loss. For further information, visit https://www.nei.nih.gov.

Treating Parkinson’s Disease with Pinpoint Precision

Parkinson’s disease affects an estimated seven to ten million people worldwide. In the United States, approximately one million people live with Parkinson’s disease. Dopamine-producing neurons in the brains of individuals with Parkinson’s disease deteriorate and stop communicating messages. People experience physical symptoms such as tremors, stiffness, and poor coordination as dopamine levels fall.

Five distinct dopamine receptors differ somewhat in structure and function. The most common drug, levodopa, or L-DOPA can worsen some movement problems when taken for long periods. That is because L-DOPA and similar medicines cannot differentiate between these receptors, so they interact with either the wrong ones or all of them simultaneously.

“That’s a problem if you’re trying to develop drugs to target individual receptor subtypes,” explains Dr. Sibley, IRP senior investigator. “Many drugs available today cross-react with other receptors, which can lead to side effects.”

IRP researchers are developing a drug that, when taken alongside other treatments, could more effectively slow the progression of Parkinson’s disease while reducing side effects. IRP scientists used high-throughput drug screening robots to sift through the nearly 400,000 compounds in NCATS’ library to find something that worked. They conducted the screen twice: once looking for ‘antagonists’ that shut down the D3 receptor and once to see that they activated the receptor-activated receptor.

“You go through many rounds of testing slightly different versions of a starting compound to see what changes on the molecule improve activity and selectivity and which changes decrease activity,” postdoctoral fellow and co-investigator Dr. Moritz explains.

The IRP researchers eventually narrowed it down to one highly selective for the D3 receptor, meaning it interacted strongly with that receptor but weakly or not at all with other types of dopamine receptors. To enhance the compound’s effects on the D3 receptor, the IRP team collaborated with Kevin Frankowski, Ph.D., a medicinal chemist at the University of North Carolina, to synthesize and test variants with minor chemical modifications. They found a drug candidate called ML417 that showed promise.

“In our manuscript, we showed that ML417 is actually the most selective D3 agonist currently known,” Dr. Sibley says. “We then worked with a computational chemist at NIH, Dr. Lei Shi, to learn why this compound is so selective. We found that it interacts with the D3 receptor in a way that is unique compared with other molecules that activate that receptor.

Because ML417 targets D3 receptors, it has significant potential as a drug to treat Parkinson’s disease-related mobility issues. The D3 receptor is predominantly expressed in the brain regions that control movement.

Although more research is needed, preliminary studies in animal models conducted in collaboration with IRP senior investigator Judith Walters, Ph.D., suggest that ML417 may have immunomodulatory effects.

The IRP team is also working with outside NIH colleagues to test the hypothesis that lowering D3 receptors can help prevent relapse in opioid pill users attempting to quit.

“Translational science is just so important,” notes Dr. Sibley. “It’s the way forward for developing novel therapeutics for treating many different diseases and disorders.”

Leveraging Turncoat Immune Cells to Combat Cancer

Macrophages are a type of white blood cell that normally help protect the body from infection and disease. They have a receptor protein on their surfaces known as CD206 that activates the phagocytosis process, which is more formally defined as ‘cell eating.’ When CD206 is activated, macrophages capture and bind to foreign threats before pushing them into their interior for digestion. However, cancer cells can push back by switching the CD206 receptor off which allows them to hijack the macrophages turning them into tumor-associated macrophages that supports tumor growth.

A new study by IRP senior investigators Udo Rudloff, M.D., Ph.D., and Juan Marugan, Ph.D. found a way to fight back against this cancer defense mechanism. The approach uses a small molecule drug to “reprogram” macrophages and other cells that have been hijacked by the tumor, restoring their anti-tumor activity.

“Initially, immunotherapy was all about immune cells such as T cells,” says Dr. Rudloff, “but in the last decade people have recognized that other cells, like these macrophages, can be very helpful as well.”

Dr. Rudloff and his research team searched the NIH’s National Center for Advancing Translational Sciences (NCATS) library of molecules for a molecule with a similar CD206. In computer modeling, they discovered a few that met this criterion. They picked one to test in animal models to see how well it worked and how long it stayed in the body before being broken down once they had narrowed down the candidate molecules to a small set.

“We were able to find molecules that worked very efficiently doing the same thing that the CD206 receptor did: activate the immune system and change the immune environment to suppress the growth of all kinds of tumors,” says Dr. Marugan. “This will be a new modality of immunotherapy using a small molecule.”

This potential new therapy also appears to be “tumor agnostic,” which means it may work on any tumor that displays a high quantity of tumor-associated macrophages with CD206 receptors. Current animal and cell studies are showing that the therapy is highly effective against pancreatic, colorectal, breast, skin malignancy melanoma, and bone cancer osteosarcoma. The researchers are now in the final stages of testing and seeking a pharmaceutical industry partner to help begin the first-in-class human clinical trials for cancer.

Reprogramming macrophages may also be beneficial in other conditions. Dr. Rudloff and Dr. Marugan are collaborating with Japanese researchers who are developing a potential therapy for diabetic retinopathy, a disease complication caused by hyperglycemia in which macrophages with the CD206 receptor play an essential role.

Trial of potential universal flu vaccine opens at NIH Clinical Center

A novel influenza vaccine has been developed by scientists at the National Institute of Allergy and Infectious Diseases (NIAID). It is now being tested in Phase 1 clinical trial at the NIH Clinical Center in Bethesda, Maryland. The safety of a candidate vaccine, BPL-1357, and its capacity to elicit immune responses will be evaluated in the study.

“Influenza vaccines that can provide long-lasting protection against a wide range of seasonal influenza viruses as well as those with pandemic potential would be invaluable public health tools,” said NIAID Director Anthony S. Fauci, M.D. “The scientific community is making progress on this pressing global health priority. The BPL-1357 candidate influenza vaccine being tested in this clinical trial performed very well in pre-clinical studies, and we look forward to learning how it performs in people.”

BPL-1357 is a “live attenuated” vaccine, meaning that it uses weakened influenza viruses to help the body build immunity against infection by natural influenza viruses. The weakened viruses in the vaccine are unable to cause illness.

An animal study by NIAID investigator Jeffery K. Taubenberger showed that mice intramuscularly or intranasally administered two doses of BPL-1357 vaccine survived exposure to each of the six different influenza virus strains and subtypes not included in the vaccine at lethal doses.

The single-site trial can enroll up to 100 people aged 18 to 55 years, will last approximately seven months for each participant, and is led by NIAID investigator Matthew J. Memoli. In the Phase 1 trial, participants will be assigned to one of three groups and given two doses of placebo or vaccine, each administered 28 days apart, in a 1:1:1 ratio. Group A gets BPL-1357 intramuscularly plus nasal saline placebo. Group B will be administered intranasal doses of the candidate vaccine with an intramuscular placebo at both visits to the clinic. In contrast, Group C gets the inactive substance injections only once. Neither the researchers nor participants are aware of group assignments. Volunteers must have not received any vaccination for the flu in the previous eight weeks and must commit to avoiding seasonal flu vaccines for two months after the second dose.

“With the BPL-1357 vaccine, especially when given intranasally, we are attempting to induce a comprehensive immune response that closely mimics immunity gained following a natural influenza infection,” said Dr. Memoli. “This is very different than nearly all other vaccines for influenza or other respiratory viruses, which focus on inducing immunity to a single viral antigen and often do not induce mucosal immunity.”

The National Institutes of Health (NIH) funds and directs research on the causes of infectious and immune-mediated diseases and develops new methods to prevent, diagnose, and treat these illnesses. For additional information about the trial, visit clinicaltrials.gov and search on the trial identifier NCT05027932.

Upcoming Events:

Health Disparities in Osteoarthritis Workshop

Tuesday, July 12, 2022, to Wednesday, July 13, 2022

Healthy Reference Tissue and Standards Workshop

Monday, July 25, 2022, 10 AM. Registration deadline: July 22, 2022

Irreducible Subjects: Disability and Genomics in the Past, Present and Future 

Thursday, October 6, 2022, 10:00 am to Friday, October 7, 2022, 5:00 pm (registration required)

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Recent NIH Research

A Computational Approach to Curbing Chemotherapy’s Side Effects

Chemotherapy can be an effective treatment for cancer, but it often comes with unpleasant side effects like nausea, vomiting, and diarrhea. Now, researchers think they may have found a way to reduce those side effects by targeting the gut microbiome.

The human gut is home to trillions of microbes, including many different species of bacteria. Some of these bacteria produce an enzyme called beta-glucuronidase that can remove a sugar molecule from chemotherapy medications, making them more active and thus more likely to cause side effects.

A cutting-edge computational technique was used in a new IRP research by Min Shen, Ph.D. who leads the Informatics group in the Division of Preclinical Innovation at NIH’s National Center for Advancing Translational Sciences (NCATS) to help identify compounds that target one of those bacterial molecules, which might lead to the development of anti-tumor medications that alleviate some chemotherapy side effects.

“Many people can’t tolerate the side effects and can’t complete the full course of their chemotherapy,” says Min Shen, Ph.D., “Normally, chemotherapy will be administered multiple times, but many people quit in the middle.”

That is why Dr. Shen’s team is attempting to discover chemicals that can stop bacterial beta-glucuronidase enzymes, which exacerbate chemotherapy’s negative effects. Her team screened more than 400,000 molecules using the computational technique and found 69 molecules that inhibited beta-glucuronidase and 13 that were very effective.

One of the chemicals discovered by Dr. Shen’s research may be developed into a drug to treat digestive issues caused by chemotherapy treatments. However, before this can happen, Dr. Shen’s team must conduct additional research as well as collaborate with chemists at NCATS to change the chemicals for better drug efficacy.

Vaccine for rare but deadly mosquito-borne viruses shows promise in clinical trial

Mosquito-borne viruses classified as potential biological warfare agents include western (WEEV), eastern (EEEV), and Venezuelan (VEEV) equine encephalitis viruses, which are viral diseases that may be spread by mosquitoes. Infection with any of these viruses can cause flu-like symptoms and even severe neurological damage or death in humans.

The WEEV, EEEV, and VEEV viruses are all classified as potential biological warfare agents due to their ability to be transferred by aerosol droplets under specific lab conditions. There is currently no vaccine or treatment available for any of these diseases, but a recent clinical trial sponsored and funded by the National Institute of Health (NIAID) has shown that a new vaccine is safe and well-tolerated.

Scientists at the NIAID Vaccine Research Center (VRC) part of the National Institutes of Health, created a virus-like particle (VLP) vaccine candidate (abbreviated WEVEE) that incorporates proteins from the EEE, WEE, and VEE viruses’ outer shells to stimulate an immune response. This response is similar to the one that would be elicited by the actual viruses but does not contain infectious material and thus poses no risk of infection.

The VRC researchers conducted a Phase I clinical trial in which 30 adult volunteers were given an initial dose of the VEVEE vaccine and a booster of the same dose 8 weeks later.  The study found that the vaccine was safe and well-tolerated with no serious adverse events reported. The participants also showed the development of EEEV, WEEV, and VEEV-specific neutralizing antibodies in their blood.

This is encouraging news and supports further clinical evaluation for the development of a potential vaccine to protect against these viruses, which have no current prevention or treatment options available.

The NIAID has granted Emergent BioSolutions, a life-sciences firm located in Gaithersburg, Maryland, a commercialization license for the advanced study of the WEVEE vaccine candidate.

Retinal cell map could advance precise therapies for blinding disease

A new study funded by the NEI Intramural Research Program and conducted by researchers from The National Eye Institute (NEI) used artificial intelligence (AI) to assess RPE cell morphometry, the external form, and the size of each cell. The Retinal Pigment Epithelium (RPE) is a layer of cells that support the function of photoreceptors, the light-sensitive cells responsible for vision.

They trained a computer to examine the entire human RPE monolayer from nine cadaver donors with no history of significant eye disease by feeding it fluorescently labeled pictures of RPE. They discovered five distinct RPE cell subpopulations, dubbed P1-P5, positioned in concentric circles around the fovea, the light-sensitive center of the macula, and the retina’s most sensitive region. Foveal RPE are typically perfectly hexagonal and compactly positioned, with more neighboring cells than peripheral RPE.

“These results provide a first-of-its-kind framework for understanding different RPE cell subpopulations and their vulnerability to retinal diseases, and for developing targeted therapies to treat them,” said Michael F. Chiang, M.D., director of the NEI, part of the National Institutes of Health.

“The findings will help us develop more precise cell and gene therapies for specific degenerative eye diseases,” said the study’s lead investigator, Kapil Bharti, Ph.D., who directs the NEI Ocular and Stem Cell Translational Research Section.

They were surprised to find that the peripheral retina contains a ring of RPE cells (P4) with a cell area comparable to that of RPE in and around the macula.

“The presence of the P4 subpopulation highlights the diversity within retinal periphery, suggesting that there could be functional differences among RPE that we are currently unaware of,” said the study’s first author, Davide Ortolan, Ph.D. a research fellow in the NEI Ocular and Stem Cell Translational Research Section.

To further test the hypothesis that various retinal diseases affect specific RPE subpopulations, they examined ultrawide-field fundus autofluorescence images from persons with choroideremia, L-ORD, or a retinal degeneration for which no molecular cause was identified. Although this research was conducted in a single setting at one point in time, it showed that various RPE subpopulations are susceptible to different types of retinal degenerative diseases.

“Overall, the results suggest that AI can detect changes of RPE cell morphometry prior to the development of visibly apparent degeneration,” said Ortolan.

Some RPE subpopulations may show age-related morphometric changes before others. These findings will aid future research utilizing noninvasive imaging technologies, such as adaptive optics, which image retinal cells at much greater resolution and might be used to predict changes in RPE health in living patients.

Reprogramming Cancer

The growth mechanism in prostate cancer is simple compared to other types of cancer. The androgen receptor, a cellular protein that testosterone must bind to function, is required for prostate cancer cells.

However, prostate cancer has proved difficult to treat because it frequently develops resistance to androgen deprivation therapy. The therapy may initially shrink the tumors, but they will eventually resurgence, at which time there is little that can be done.

David Takeda, M.D., Ph.D., a researcher at the Intramural Research Program (IRP), is developing a new strategy to treat cancer that relies on epigenetic manipulation. He thinks that changing epigenetics may provide an effective new approach to treatment.

“Prostate cancer is not like other cancers where we don’t know what the main driver is,” Dr. Takeda says. “In prostate cancer, we know the androgen receptor is the main driver, but even though we know that, we still can’t cure it.”

Dr. Takeda is now working to study further his discovery conducted at the Dana-Farber Cancer Institute in Boston, Massachusetts, which showed that shutting down the regulatory region in prostate cancer cells (enhancer) slows down cancer growth.

“Can you tell a cancer cell what to do?” wonders Dr. Takeda. “It would be really cool if you could program a cancer cell to do something. You could dictate its identity epigenetically, and maybe you could change it to a state that’s amenable to treatment or a state where it doesn’t grow, but we don’t yet know if that’s possible.”

“That’s kind of what NIH is for: to try out these big ideas to see if they could possibly work,” he continues. “If it turns out to not work, at least we thought big.”

Dr. David Takeda is a Lasker Clinical Research Scholar and the director of the Functional Genomics Section in the Laboratory of Genitourinary Pathogenesis at the National Cancer Institute (NCI).

The Center for Cancer Research (CCR) was founded to educate and empower the entire cancer research community by making essential discoveries in basic and clinical cancer research and developing them into innovative treatments for individuals afflicted with cancer or infected with HIV. To learn more about the Center for Cancer Research, visit their website.

Viruses on the Brain

Viruses may cause long-term damage to the brain, even when a person is not actively sick.

Dr. Avindra Nath is the Clinical Director at the National Institute of Neurological Disorders and Stroke (NINDS) and the head of its Section of Infections of the Nervous System. His lab focuses on understanding the pathophysiology of retroviral infections of the nervous system and the development of new diagnostic and therapeutic approaches for these diseases.

Dr. Nath’s team has discovered a protein in the brains of HIV-positive patients, even when antiretroviral therapy has reduced the amount of HIV in their blood to undetectable levels. The team’s work has also suggested that this protein, known as Tat, could be responsible for the neurological problems seen in some HIV-positive patients. He believes that HIV lives in brain cells and is unaffected by antiretroviral medications, continuing to produce Tat and causing brain inflammation and neuron death.

Dr. Nath and his team are working on creating single-stranded, DNA-like molecules called antisense oligonucleotide that can target and silence the gene that encodes Tat. The lab is also studying ‘checkpoint inhibitors, drugs that have recently been used in cancer immunotherapy.

“The common thread among all of these illnesses is their under-recognized effects on the brain,” Dr. Nath says. “What happens with most pandemics and viral infections is that people get focused on the effects on the organ system that causes the acute symptoms,” he says. “If patients forget things or are not behaving normally, their doctors just blame some other explanation for it rather than thinking that the disease itself might be the cause.”

Similarly, they have found evidence of brain damage in deceased COVID-19 patients, suggesting that the virus can cause long-term problems even after a person has recovered from the acute illness.

Discoveries like those being conducted in Dr. Nath’s lab have the potential to revolutionize how viral infections are treated long-term.

“You have to be very careful,” he says. “People who had COVID-19, this serious respiratory illness, are also complaining of neurological symptoms, and these symptoms may actually be persistent. We have to pay attention to this and not ignore it.”

Upcoming Events:

Sex/Gender-Specific COVID-19 Outcomes Relevant for HLBS Disorders

Thursday, June 16, 2022, 11:00 am to Friday, June 17, 2022, 5:30 pm (registration required)

Advancing Research on Emotional Well-Being and Regulation of Eating

Thursday, June 23, 2022, 12:00 p.m. ET to 1:00 p.m. ET

NIH OBSSR Director’s Webinar: Guest Presenter Irene Dankwa-Mullan M.D., M.P.H. (July 19, 2022)

July 19, 2022, 2:00 – 3:00pm | Online

Irreducible Subjects: Disability and Genomics in the Past, Present and Future 

Thursday, October 6, 2022, 10:00 am to Friday, October 7, 2022, 5:00 pm (registration required)

The post National Institutes of Health (NIH) Research Updates – June 2022 appeared first on Astrix.

Recent NIH Research

NIH researchers develop first stem cell model of albinism to study related eye conditions

Oculocutaneous albinism (OCA) is a group of inherited disorders characterized by the reduction of pigmentation in the eye, skin, and hair resulting from mutations in the genes that are responsible for melanin pigment production. Abnormalities caused by a lack of sufficient melanin pigment production include vision problems and susceptibility to sun damage to the skin.

Researchers at the National Eye Institute (NEI) have developed the first patient-derived stem cell model for studying eye conditions related to OCA. “This ‘disease-in-a-dish’ system will help us understand how the absence of pigment in albinism leads to abnormal development of the retina, optic nerve fibers, and other eye structures crucial for central vision,” said Dr. Aman George, staff scientist in the NEI Ophthalmic Genetics and Visual Function Branch, and the lead author of the report.

Pigment is present in the retinal pigment epithelium (RPE) of the eye which aids vision by preventing the scattering of light. Scientists think that RPE plays a key role in forming these structures and want to better understand how lack of pigment affects their development. People with OCA have misrouted optic nerve fibers, lack pigmented RPE, and have an underdeveloped fovea, an area within the retina that is necessary for central vision. Scientists think that RPE plays a role in forming these structures and want to understand how lack of pigment affects their development.

“Treating albinism at a very young age, perhaps even prenatally, when the eye’s structures are forming, would have the greatest chance of rescuing vision,” said Dr. Brian Brooks, NEI clinical director and chief of the Ophthalmic Genetics and Visual Function Branch “In adults, benefits might be limited to improvements in photosensitivity, for example, but children may see more dramatic effects.” The team is now exploring how to use their model for high-throughput screening of potential therapies for the treatment of OCA.

Oral immunotherapy induces remission of peanut allergy in some young children

Peanut allergy, one of the most common food allergies, affects about 2% of children in the United States, or nearly 1.5 million individuals under the age of 18. Exposure to even a small amount of peanut protein can lead to a life-threatening allergic reaction know as anaphylaxis.

In a recent clinical trial funded by the National Institutes of Health (NIH), a team of researchers concluded that providing peanut oral immunotherapy to highly peanut-allergic children safely desensitized the majority of them to peanut protein and induced remission of peanut allergy in one-fifth of the study participants. Nearly 150 children ages 1 to 3 years took part in the IMPACT trial at five academic medical centers in the United States. Only children who had an allergic reaction after eating half a gram of peanut protein or less were eligible to join the study.

The immunotherapy consisted of a daily oral dose of peanut flour for 2.5 years. Remission was defined as being able to eat 5 grams of peanut protein, equivalent to 1.5 tablespoons of peanut butter, without having an allergic reaction six months after completing immunotherapy. The youngest children and those who started the trial with lower levels of peanut-specific antibodies were most likely to achieve remission.

The research team found two key predictive factors that a child would achieve remission following the therapy: lower levels of peanut-specific immunoglobulin E antibodies at the start of the trial and being younger in age. The study data indicated an inverse relationship between age at the start of the trial and remission, with 71% of the 1-year-olds, 35% of the 2-year-olds and 19% of the 3-year-olds experiencing remission.

“The landmark results of the IMPACT trial suggest a window of opportunity in early childhood to induce remission of peanut allergy through oral immunotherapy,” said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID). “It is our hope that these study findings will inform the development of treatment modalities that reduce the burden of peanut allergy in children.” NIAID sponsored the trial and funded it through its Immune Tolerance Network.

NIH study classifies vision loss and retinal changes in Stargardt disease

In a recent study conducted by the National Eye Institute (NEI), a team of researchers developed an artificial-intelligence-based method to evaluate patients with Stargardt, an inherited an eye disease that begins in childhood and leads to the progressive loss of vision. An estimated 1 in 10,000 people have Stargardt disease. This novel method quantifies disease-related loss of light-sensing retina cells that will enable a better understanding of the genetic causes of the disease and insights into the development of therapies for the treatment of the disease.

The most common form of Stargardt is ABCA4-associated retinopathy, an autosomal-recessive disease caused by variants to the ABCA4 gene, which contains genetic information for a transmembrane protein in light-sensing photoreceptor cells. People develop Stargardt when they inherit two mutated copies of ABCA4, one from each parent. People who have just one mutated copy of ABCA4 are genetic carriers, but do not develop the disease. More rare forms of Stargardt are associated with variants of other genes.

Among patients who all have ABCA4 gene variants, there can be a wide spectrum in terms of age of onset and disease progression.

“Different variants of the ABCA4 gene are likely driving the different disease characteristics, or phenotypes. However, conventional approaches to analyzing structural changes in the retina have not allowed us to correlate genetic variants with phenotype,” said the study’s co-leader, Dr. Brian Brooks, chief of the NEI Ophthalmic Genetics & Visual Function Branch. Dr. Brooks co-led the study with Dr. Brett Jeffrey, head of the Human Visual Function Core of the NEI’s Ophthalmic Genetics and Visual Function Branch.

The study followed 66 Stargardt patients for a period of five years using a retinal imaging technology called spectral-domain optical coherence tomography (SD-OCT). The 3D cross-sectional retinal images were and analyzed using deep learning, a type of artificial intelligence (AI) in which vast amounts of imaging data can be fed into an algorithm, which then learns to detect patterns that allow the images to be classified. This methodology allowed the researchers to quantify and compare the loss of photoreceptors and various layers of the retina according to the patient’s phenotype and ABCA4 variant and provided a way of classifying the severity of 31 different ABCA4 variants.

“These results provide a framework to evaluate Stargardt disease progression, which will help control for the significant variability from patient to patient and facilitate therapeutic trials,” said Dr. Michael Chiang, director of the NEI.

Researchers highlight COVID-19 neurological symptoms and need for rigorous studies

Acute COVID-19 infection, caused by the SARS-CoV-2 virus, can sometimes lead to long-lasting effects, collectively termed as “Long Covid”. This can include a wide variety of symptoms in the brain and nervous system that range from a loss of taste and smell, impaired concentration, fatigue, pain, headache, sleep disorders, and autonomic disorders to psychological effects such as depression or psychosis.

Although SARS-CoV-2 was initially identified as a respiratory virus, it can affect the entire body. Neurological symptoms that have been reported with acute COVID-19 include loss of taste and smell, headaches, stroke, delirium, and brain inflammation. There does not seem to be extensive infection of brain cells by the virus, but the neurological effects may be caused by immune activation, neuroinflammation, and damage to brain blood vessels.

In a recent Viewpoint published in Science by Dr. Avindra Nath, clinical director of the National Institutes of Health’s National Institute of Neurological Disorders and Stroke (NINDS), and Dr. Serena Spudich, Yale School of Medicine, highlight current scientific insights surrounding the effects of SARS-CoV-2 on the brain, and how physiological responses to acute COVID-19 infection could lead to Long Covid symptoms. Dr. Nath and Dr. Spudich also outline common risk factors between individuals with Long Covid and those living with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or post-Lyme disease.

The authors emphasize the need for the further study of individuals with Long Covid, categorized by their specific symptoms, as being crucial to the development of diagnostic and therapeutic tools to identify and treat what is becoming a significant public health concern.

NIH launches first phase of $9.8 million competition to accelerate development of neuromodulation therapies

The National Institutes of Health (NIH) has launched the first phase of the Neuromod Prize, a $9.8 million competition dedicated to accelerating the development of targeted neuromodulation therapies. The Neuromod Prize is part of the SPARC (Stimulating Peripheral Activity to Relieve Conditions) initiative from the NIH Common Fund and focuses on novel uses of peripheral nerve stimulation treatments that selectively target multiple organs and functions. The competition seeks scientists, engineers, and clinicians to submit innovative concepts and clinical development plans to demonstrate solutions for precisely stimulating the peripheral nervous system to treat disease and improve human health.

The first phase of the competition (Concepts and plans for development) will select up to eight winners who will receive a share of the up to $800,000 prize pool and will exclusively be invited to participate in phase two of the competition. The second phase (Proof-of-concept studies) will award a planned prize pool of $4 million. Up to four winners from the second phase may be selected to continue on to phase three (IDE-enabling studies), awarding up to $5 million. The competition is subject to change along with the availability of funds. Details surrounding phases two and three are expected to be announced at a future date.

“Through the Neuromod Prize, we’re asking potential solvers to use the foundational knowledge and technologies that have come out of our SPARC program and take it to the next level with their innovative concepts and ideas,” said ​​Dr. James Anderson, director of the Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI), which oversees the NIH Common Fund. “This competition is an exciting opportunity to come up with tangible plans for harnessing the power of the body’s electrical system to help transform treatments for millions of people living with chronic or acute illnesses.”

For more information about the Neuromod Prize, visit neuromodprize.com.

Upcoming Events:

NCI Myelodysplastic Syndromes Symposium

Friday, February 25, 2022, 12:30 pm (register by February 21)

Rare Disease Day at NIH

Monday, February 28, 2022, 10:00 am to 6:00 pm

Leveraging the Intramural Research Program to Effect Foundational Progress in Neurodegenerative Disease\

Wednesday, March 30, 2022, 3:00 pm to 4:00 pm

Hereditary Gastric Cancer Symposium

Monday, April 4, 2022 to Tuesday, April 5, 2022 (registration required)

RNA Imaging and Intracellular Dynamics Workshop

Tuesday, April 26, 2022 (registration required)

The post National Institutes of Health (NIH) Research Updates – February 2022 appeared first on Astrix.

Recent NIH Research

A high-fiber diet may lead to an improved immunotherapy response in melanoma patients

IRP Scientists have determined that a high-fiber diet may improve the immunotherapeutic response from patients being treated for melanoma. A recent study led by the Center for Cancer Research at the National Cancer Institute (NCI) in collaboration with the University of Texas MD Anderson Cancer Center focused on the ability of the gut microbiome to modulate the immune system thereby having the potential to influence the therapeutic response of cancer patients.

Immune checkpoint inhibitors have shown significant promise in the treatment of melanoma and other difficult to treat cancers, improving the longevity of people with advanced stages of the disease by restoring the immune system’s natural ability to recognize and kill tumor cells.

In this study, patients with advanced melanoma who underwent immunotherapy with immune checkpoint inhibitors who consumed at least 20 grams a day of dietary fiber survived the longest without progression of the disease than those who consumed less dietary fiber. Every 5-gram increase in daily dietary fiber intake corresponded to a 30% lower risk of progression of the disease. In contrast, the use of probiotics, which are supplements containing live microorganisms typically consumed to improve gut health, somewhat decreased the effectiveness of immune checkpoint inhibitor regimens.

“The data suggest that one can target the composition of the gut microbiota and affect the ability of the patient to respond to immunotherapy,” said Dr. Giorgio Trinchieri, chief of the Laboratory of Integrative Cancer Immunology at NCI and coleader of the study.  “Consuming a diet rich in fiber, like fruits, vegetables, and legumes, could improve your ability to respond to immunotherapy. The data also suggest that it’s probably better for people with cancer receiving immunotherapy not to use commercially available probiotics.”

Suppressing a blood-clotting protein prevents gum disease in mice

A new study led by the National Institute of Dental and Craniofacial Research (NIDCR) suggests that suppressing the abnormal activity of fibrin, a blood-clotting protein, may lead to the prevention or treatment of periodontal disease. Nearly 50% of adults over the age of 30 and greater than 70% of adults over age 65 have some form of periodontal disease. Bacteria in the mouth can infect the tissue surrounding a tooth, causing inflammation in its early stages. As periodontal progresses, the underlying bone becomes damaged, leading to tooth loss.  The advanced stage of this disease, called periodontitis, is driven in part of an elevated immune cell response. Until now it has been unclear what triggered this response and the mechanism by which it caused tissue and bone damage.

Fibrin normally plays a protective role at sites of injury of inflammation by helping to form blood clots and activating immune cells to fight infection. However, the buildup of excess fibrin has been linked with health problems, including a rare form of periodontitis due to a condition called plasminogen (PLG) deficiency. In affected people, mutations in the PLG gene lead to the accumulation of fibrin at various body sites, including the mouth.

To explore the connection between abnormal fibrin buildup and periodontitis, the research team, led by NIDCR investigators Dr. Niki Moutsopoulos and Dr. Thomas Bugge studied PLG deficiency in mice and performed a genetic analysis of over 1,000 people. Their findings concluded that even in the absence of PLG deficiency, variations in the PLG gene were linked to an increased risk of severe periodontitis, consistent with the idea that similar processes contribute to rare and common forms of the disease. The study further suggests that excessive buildup of fibrin in the gums—whether due to changes in genes like PLG, chronic inflammation from a bacterial infection, or some combination of the two—triggers an elevated and ultimately harmful neutrophil response that causes periodontal disease.

NIH researchers identify potential AMD drugs with stem cell-based model

Researchers at the National Eye Institute (NEI) have identified two promising drug candidates that may slow dry age-related macular degeneration (AMD), a leading cause of blindness for which no permanent cure exists. Dry AMD is when parts of the macula become thinner with age and tiny clumps of protein called drusen form causing the progressive loss of central vision.

Two of the drugs tested prevented the stem cell model from accumulating drusen, lipid-rich deposits in the retina, and the atrophy, or shrinkage, of retinal pigment epithelium (RPE) cells. RPE is a layer of tissue that nourishes the retina’s light-sensing photoreceptors. In AMD, RPE cells shrink and die leading to the death of photoreceptors and ultimately to loss of vision.

The research team led by Dr. Kapil Bharti, director of the NEI Ocular and Stem Cell Translational Research Section, and Dr. Ruchi Sharma, staff scientist in the lab and lead author of the paper, developed the experimental model using stem cell-derived mature RPE cells. Dr. Bharti’s group initially developed the cells using skin fibroblasts or blood samples donated from AMD patients. The fibroblasts or blood cells were programmed to become induced pluripotent stem cells (iPSC), and then programmed again to become RPE cells.

In the study, more than 1,200 drugs were screened via the stem cell model from a library of pharmacological agents that had been tested for a range of other conditions. Two drugs were flagged for their ability to inhibit RPE atrophy and drusen formation: A protease inhibitor called aminocaproic acid, which likely directly blocks the complement pathway outside cells and L745, which was originally tested by Merck & Co. for treating schizophrenia.  L745 stops complement induced inflammation inside the cell indirectly via inactivation of the dopamine pathway.

“This stem cell-derived model of dry AMD is a game-changer. Scientists have struggled to unravel this incredibly complex disease, and this model could prove to be invaluable for understanding the causes of AMD and discovering new therapies,” said Dr. Michael Chiang, director of the NEI.

NIH study suggests women with disabilities have increased risk of birth complications

In new study conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), researchers have determined that pregnant women with disabilities have an increased risk for a broad spectrum of pregnancy and birth related complications, including mortality.

Based upon an analysis of more than 223,000 deliveries in 19 U.S. hospitals, approximately 2,199 pregnant women had a physical, sensory or intellectual disability. Compared to women without disabilities, women with disabilities had:

• Greater than twice the risk for severe preeclampsia
• 48% higher risk for mild preeclampsia
• 25% higher risk for gestational diabetes
• 52% higher risk for placenta previa
• 16% higher risk for premature rupture of the membranes
• 27% higher risk for hemorrhage
• 11 times the risk for maternal death
• more than six times the risk for blood clots
• four times the risk for cardiovascular events, such as heart attacks
• nearly three times the risk for infection
• 33% greater likelihood of receiving the drug oxytocin to stimulate labor, delivery with forceps or other devices to extract the fetus, or cesarean delivery

“Additional research is needed to understand the reasons for this increased risk and to develop needed interventions to reduce it,” said Dr. Jessica Gleason, NICHD research fellow and lead author of the study. The authors noted that women with disabilities are more likely to live in poverty, which may make accessing health care in a timely manner difficult. Other factors that may increase their health risks are higher rates of smoking, substance use and depression.

Experimental mRNA HIV vaccine shows promise in animals

An experimental HIV vaccine shows promise in mice and non-human primates, according to researchers at the National Institute of Allergy and Infectious Diseases (NIAID). Based upon this new study, the vaccine was determined to be safe and triggered an antibody response against an HIV-like virus. Rhesus macaques receiving a priming vaccine followed by multiple booster inoculations had a 79% lower per-exposure risk of infection by simian-human immunodeficiency virus (SHIV) compared to unvaccinated animals.

“Despite nearly four decades of effort by the global research community, an effective vaccine to prevent HIV remains an elusive goal,” said Dr. Anthony Fauci, NIAID Director, chief of the Laboratory and co-author of the paper. “This experimental mRNA vaccine combines several features that may overcome shortcomings of other experimental HIV vaccines and thus represents a promising approach.”

The research team, led by Dr. Paolo Lusso, of NIAID’s Laboratory of Immunoregulation, in collaboration with other NIAID scientists, investigators from Moderna, Inc. and colleagues at other institutions, developed an mRNA vaccine that delivers coded instructions for making two key HIV proteins, Env and Gag. Muscle cells in an inoculated animal assemble these two proteins to produce virus-like particles (VLPs) studded with numerous copies of Env on their surface. The Env proteins produced in the mice from the mRNA instructions closely resembled those in the whole virus, an improvement over previous experimental HIV vaccines.

After 13 weekly inoculations, two out of seven immunized macaques remained uninfected, while the other immunized animals had an overall delay in infection, which occurred, on average, after eight weeks. In contrast, unimmunized animals became infected on average after three weeks. Dr. Lusso noted, “The display of multiple copies of authentic HIV envelope protein on each VLP is one of the special features of our platform that closely mimics natural infection and may have played a role in eliciting the desired immune responses.”

Upcoming Events:

NIH Workshop on Psychedelics as Therapeutics: Gaps, Challenges and Opportunities

Wednesday, January 12, 2022, 9:00 am to Thursday, January 13, 2022, 2:55 pm (registration required)

Technology to Improve Maternal Health

Tuesday, January 18, 2022, 12:00 pm to 6:30 pm (registration required)

The Centriculum: a Centrosome Associated Membrane Reticulum That Affects Centrosome Structure and (maybe) Centrosome Nuclear Envelope Interactions

Tuesday, January 25, 2022,  12:00 pm to 1:30 pm

NCI Myelodysplastic Syndromes Symposium

Friday, February 25, 2022, 12:30 pm (register by February 21)

Rare Disease Day at NIH

Monday, February 28, 2022, 10:00 am to 6:00 pm

Hereditary Gastric Cancer Symposium

Monday, April 4, 2022 to Tuesday, April 5, 2022 (registration required)

RNA Imaging and Intracellular Dynamics Workshop

Tuesday, April 26, 2022 (registration required)

The post National Institutes of Health (NIH) Research Updates – January 2022 appeared first on Astrix.

Recent NIH Research

ALS drug shows promise in mouse model of rare childhood genetic disorder

New IRP research showed promising results for slowing the progression of Niemann-Pick disease type C1 (NPC1) using riluzole, an FDA approved drug for the treatment of amyotrophic lateral sclerosis (ALS). Niemann-Pick disease type C1 is an inherited, neurogenerative disorder that causes a massive accumulation of lipids in the liver, brain, spleen and bone marrow. Approximately 50% of cases of NPC1 present in childhood, before 10 years of age. There is no known cure for this fatal disease, other than symptomatic relief.

This rare metabolic disorder leads to the progressive deterioration of the nervous system and loss of function of the brain and other organs. NPC1 results from the impaired ability to transport cholesterol and other lipids through cells, leading to difficulty controlling movements, liver and lung disease, impaired swallowing, intellectual decline and death. Much of the movement difficulties in NPC1 result from a gradual loss of brain cells known as Purkinje neurons.

The collaborative study was conducted by Dr. Forbes Porter, senior investigator at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and colleagues in the National Human Genome Research Institute (NHGRI) and National Institute of Arthritis and Musculoskeletal and Skin Disease (NIAMS).

The team of researchers discovered that mice with a form of NPC1 have a diminished ability to lower the levels of glutamate, a brain chemical that stimulates neurons after it has bound to a neuron’s surface. The team believes that the buildup of glutamate contributes to the brain cell loss seen in the disease, as high levels of glutamate are known to cause cell toxicity.

Riluzole, while it is not a cure for ALS, delays the progression of the disease in humans by blocking the release of glutamate. As part of the current study, mice with NPC1 that were treated with riluzole had a survival rate of 12% longer than untreated mice. The research team hypothesizes that riluzole or similar drugs may provide a viable way to slow disease progression in patients with NPC1.

Inflammation Contributes to Cancer-Related Fatigue

A recent IRP study led by the National Institute of Nursing Research (NINR) suggests that intense exhaustion experienced by cancer patients may be caused in part by inflammation resulting from radiation therapy.

Chemotherapy, a drug therapy used to stop the growth of cancer cells and prevent them from spreading, introduces potent chemicals into the bloodstream. Since chemotherapy effects healthy cells as well as cancer cells, it can cause extreme fatigue as the body fights to repair the damage caused by the treatment. Total body irradiation is known to have severe side effects include excessive fatigue or tiredness. However, even when radiation is targeted to just one area, it can still lead to debilitating cancer-related fatigue.

Dr. Leorey Saligan, senior investigator at NINR has studied the effect of targeted radiation treatment on patients with prostate cancer and noted that while they initially do not experience cancer-related fatigue, they do, however, develop debilitating fatigue following radiation treatment targeted to the prostate. As many as 40% of the treated patients will continue to experience chronic fatigue for as long as one to two years after the end of their treatment period.

As patients in the study had not reported experiencing fatigue from the cancer itself, Dr. Saligan and his research team investigated how the radiation treatment might be a cause of the extreme fatigue. Although there have been frequent reports of significant inflammation in patients with cancer-related fatigue, none had determined this to be the potential source of the fatigue.

The researchers used a mouse model of cancer-related fatigue to further explore the effects of inflammation following radiation treatment. In this study, it was noted that healthy male mice that received radiation targeted to the pelvis spent significantly less time running on their wheels than control mice not exposed to radiation. However, mice that were given minocycline, an antibiotic that also reduces inflammation, showed a noticeably smaller decrease in their wheel running than mice not given the antibiotic, though they still ran much less than mice that were not exposed to radiation. Similarly, after pelvic radiation treatment, mice lacking a gene involved in the body’s inflammatory response ran more on their wheels than genetically normal mice.

“This is a big first step to really show some causality between fatigue and inflammation,” says Dr. Saligan. “We’re hoping that with these initial results that show a causal relationship, we can provide avenues to address the role of inflammation in cancer-related symptoms such as fatigue.”

Extreme eating problems in early childhood linked to increased likelihood of developmental delay

Researchers at the Epidemiology Branch of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) have determined that young children with a history of eating problems during their first three years of life had a higher likelihood of receiving low scores on assessments of child development.

The findings suggest that children with multiple eating problems such as frequent crying during meals, pushing food away, and gagging while eating may benefit from screening for developmental delay. Early diagnosis of developmental disorders is key to getting children the help they need.

In this new study, led by IRP scientist Dr. Diane Putnick, NICHD, a team of researchers analyzed data on more than 3,500 children from Upstate KIDS, a study of children born between 2008 and 2010 in New York State. Mothers responded to questionnaires, rating their children’s eating patterns and developmental milestones when the children were 18, 24 and 30 months old. Compared to children who did not have eating problems, those who scored high on eating problems at one or two time points were more than twice as likely to miss a developmental milestone. Children with feeding problems at all three ages were four or more times as likely to miss a milestone.

The researchers noted that while feeding problems are not likely the cause of developmental delay, the problems associated with developmental delay, such as undiagnosed neurological issues, communication difficulties or lack of fine motor skills may underlie feeding problems. Children with feeding problems only at 18 and 24 months could potentially be the result of temporary variations in maturation, while feeding problems that persist until 30 months are at greatest risk for developmental delay and are the strongest candidates for screening.

Researchers target a mouse’s own cells, instead of antibiotics, to treat pneumonia

Researchers at the National Institute of Environmental Health Sciences (NIEHS) have discovered a novel method for the treatment of pneumococcal pneumonia, the leading cause of pneumonia deaths worldwide as reported by the World Health Organization (WHO).

While antibiotics are prescribed as the common course of treatment for bacterial pneumonia, caused by Streptococcus pneumoniae, the treatment is not always successful, and in some cases the bacteria even become resistant.

IRP scientist and co-lead author of the study, Dr. Matthew Edin, wanted to find a way to augment the body’s own immune system as an alternative method to resolve the infection. The research team focused on developing a therapy targeting host cells rather than bacterial cells in rodents.

To keep tissues healthy, epoxyeicosatrienoic acids (EETs) work to limit inflammation within the body, but during infections, such as bacterial pneumonia, inflammation ramps up after lung cells induce certain substances that prompt macrophages to digest the bacteria. The research team found that one way to get macrophages to eat more bacteria is to decrease the ability of EETs to limit inflammation. Using a synthetic molecule called EEZE to block EET activity boosted the eating capacity of the macrophages, leading to a reduction in the amount of bacteria in the lungs of mice. The scientists saw the same result when they placed bacteria and macrophages harvested from lung and blood samples of human volunteers in test tubes at the NIEHS Clinical Research Unit.

“EEZE is safe and effective in mice, but scientists could develop similar compounds to give to humans,” said Dr. Edin. “These new molecules could be used in an inhaler or pill to promote bacterial killing and make the antibiotics more effective.”

Repurposed cancer treatments could be potential Alzheimer’s drugs

According to a recent IRP study, existing and emerging cancer drugs showed promise for being repurposed as therapies to be tested in clinical trials for people at genetic risk of Alzheimer’s disease. The analysis of brain protein alterations in these individuals as well as laboratory experiments in animal models and cell cultures could assist scientists in quickly identifying existing drugs to test their potential as Alzheimer’s interventions.

Researchers from the National Institute on Aging (NIA) in collaboration with NIA-supported teams at the University of California, San Francisco; Rush University, Chicago; and the Icahn School of Medicine at Mount Sinai, New York City identified brain protein changes related to the APOE4 genetic risk variant in young postmortem study participants (average age at death was 39 years) and compared these changes with those in the autopsied brains of people with Alzheimer’s and those without (average age at death was 89 years). The analyses included brain samples from the Baltimore Longitudinal Study of Aging, the Religious Orders Study, and other NIA-funded studies. Existing FDA-approved or experimental drugs for other diseases were then tested for activity upon these proteins.

Their findings show that an experimental drug for the treatment of liver cancer and Dasatinib, an approved for chronic myeloid leukemia, was found to act upon some of the Alzheimer’s disease related proteins, suggesting they could be potential Alzheimer’s therapies. The drugs also reduced neuroinflammation, amyloid secretion, and tau phosphorylation in cell culture experiments, underscoring their potential as candidates to be tested in Alzheimer’s clinical trials.

Lung autopsies of COVID-19 patients reveal treatment clues

Scientists at the National Institutes of Health and their collaborators have a clearer picture of how SARS-CoV-2, the virus that causes COVID-19 disease, spreads and damages lung tissue. These important findings could assist in predicting severe and prolonged cases of COVID-19 and inform effective treatments, particularly among those at high risk.

A small study using lung and plasma samples autopsied from people who died of COVID-19 and had at least one high-risk condition such as diabetes, obesity or being elderly, revealed trends that could help develop new COVID-19 therapeutics and fine-tune when to use existing therapeutics at various stages of disease progression or caring for high-risk patients. The findings of the study include details about how SARS-CoV-2 spreads in the lungs, manipulates the immune system, causes widespread thrombosis that does not resolve, and targets signaling pathways that promote lung failure, fibrosis and impair tissue repair.

The study included patients who died between March and July 2020, with time of death ranging from 3 to 47 days following the onset of symptoms. This enabled the scientists to compare short, intermediate, and long-term cases. Every case showed findings consistent with diffuse alveolar damage, which prevents proper oxygen flow to the blood and eventually makes lungs thickened and stiff. The scientists also determined that SARS-CoV-2 directly infected basal epithelial cells within the lungs, impeding their essential function of repairing damaged airways and lungs and generating healthy tissue. The process is different from the way influenza viruses attack cells in the lungs, which provides scientists with additional information to use in the development of antiviral therapeutics.

Researchers at the National Institute of Allergy and Infectious Diseases (NIAID) led the project in collaboration with the National Institute of Biomedical Imaging and Bioengineering | (nih.gov) and the FDA. Other collaborators included the Institute for Systems Biology in Seattle; University of Illinois, Champaign; Saint John’s Cancer Institute in Santa Monica, California.; the USC Keck School of Medicine in Los Angeles; University of Washington Harborview Medical Center, Seattle; University of Vermont Medical Center, Burlington; and Memorial Sloan Kettering Cancer Center in New York City.

Upcoming Events:

Building Unifying Systems of Care Addressing Comorbidities in Women and Girls

Thursday, December 16, 2021, 11:00 am to Friday, December 17, 2021, 5:30 pm (register by December 10)

NIH Workshop on Psychedelics as Therapeutics: Gaps, Challenges and Opportunities

Wednesday, January 12, 2022, 9:00 am to Thursday, January 13, 2022, 2:55 pm (registration required)

Technology to Improve Maternal Health

Tuesday, January 18, 2022, 12:00 pm to 6:30 pm (registration required)

RNA Imaging and Intracellular Dynamics Workshop

Tuesday, April 26, 2022 (registration required)

The post National Institutes of Health (NIH) Research Updates – December 2021 appeared first on Astrix.

The National Institutes of Health (NIH) is our nation’s medical research agency. Its mission focuses on scientific discoveries that improve health and save lives. Founded in 1870, the NIH conducts its own scientific research through its Intramural Research Program (IRP), which supports approximately 1,200 principal investigators and more than 4,000 postdoctoral fellows conducting basic, translational and clinical research. In this blog, we will highlight recent innovative NIH research.

IRP’s Steven Rosenberg receives HHS Secretary’s Award for Distinguished Service

Dr. Steven Rosenberg, Chief of Surgery at the National Cancer Institute, has been awarded the HHS Secretary’s Award for Distinguished Service in recognition of his groundbreaking research in cancer immunotherapy. He pioneered the development of immunotherapy, resulting in the first effective immunotherapy for selected patients with advanced stage cancer. Dr. Rosenberg is the first researcher to successfully insert foreign genes into humans, leading to the development of gene therapy as a novel technique in the treatment of disease. The award, which celebrates excellence in leadership, ability, and service, is the highest honor given by the US Department of Health and Human Services.

Throughout his 47 year career at NCI, Dr. Rosenberg has been at the forefront of using immunotherapy and gene therapy to treat multiple forms of cancer, including kidney cancer, lymphoma, and melanoma. This innovative treatment directly targets tumors without the destruction of healthy tissue that occurs with traditional methods such as surgery, chemotherapy and radiation treatment. “One of the major advantages of immunotherapy is it can be highly specific in its recognition of affected cells,” Dr. Rosenberg explains. The therapies based upon his work have even proven capable of combating ‘metastatic’ cancers that have spread around the body from the site where they first developed.

As a young surgical resident at what is now Brigham and Women’s Hospital in Boston, Dr. Rosenberg was assigned to work at the VA Hospital in West Roxbury. There, he encountered a patient who needed his gallbladder removed, but a quick review of the patient’s medical records showed something very unusual. Twelve years earlier, the patient had undergone surgery to remove a stomach tumor. The notes indicated that several tumors couldn’t be removed, and the patient had received no further treatment. Yet when Dr. Rosenberg performed the gallbladder surgery, there was no sign of the old cancer.

“It’s one of the rarest events in medicine,” Dr. Rosenberg says. “Somehow his body had learned to defeat the disease, and it seemed likely to me that the immune system was responsible.”

In another case that occurred during his residency, Dr. Rosenberg saw a patient that had received a donated kidney that his doctors later learned contained cancerous cells. With the patient’s immune system disabled so his body would not reject the new kidney, the cancer quickly spread. When his doctors discontinued the immunosuppressive drug regimen, the patient’s body rejected the kidney, as expected, but surprisingly also started attacking the cancer, including the cancer cells that had spread from the donated organ. “That demonstrated to me that if you have a strong enough immune stimulus, the body was capable of rejecting even large, invasive cancers,” Dr. Rosenberg explains.

After joining the NIH in 1974, Dr. Rosenberg focused his work on studying immune cells called lymphocytes, which are white blood cells that fight infection. His research team determined they could remove lymphocytes that had infiltrated the tumor and were already fighting the cancer and treat the extracted cells in in the lab with a hormone naturally produced in the body called interleukin-2 (IL-2), which stimulated them to multiply 1,000-fold. These treated cells could then be injected back into the patient, where they found their way to the tumor and stepped up their attack. “This concept of using the body’s own immune cells as a drug has been the underlying basis of virtually everything I’ve done,” says Dr. Rosenberg.

The first immunotherapies approved for cancer treatment were based upon Dr. Rosenberg’s research with IL-2. In 1985, his team showed that giving patients that hormone could cause tumors to shrink in about 20 percent of people with melanoma and metastatic kidney cancer, with about one-third of those responding to the treatment showing no signs of cancer afterward. The FDA approved IL-2 immunotherapy for kidney cancer in 1992 and for melanoma in 1998.

More recently, Dr. Rosenberg and his team have been developing gene therapies that modify the patient’s own immune cells so that they can more effectively recognize and attack cancer, leading to the 2017 FDA approval of the first-ever gene therapy for cancer. Dr. Rosenberg’s team has also identified hundreds of unique antigens that immune cells could potentially use to identify and attack cancer cells. “These antigens are unique to each individual, so targeting them has to be highly personalized,” he says. Dr. Rosenberg’s team is now working on ways to efficiently produce the modified immune cells needed for this type of treatment and applying it to other cancers such as leukemia and lymphoma.

“This award is a recognition not only of what I’ve done,” Dr. Rosenberg says, “but also an indication and inspiration to continue to make progress toward the goal of developing new immunotherapies for patients with cancer.”

To boost learning, timing may be everything

In a new study, IRP researchers have discovered that transcranial magnetic stimulation (TMS), a noninvasive method of brain stimulation, significantly boosts motor skill learning when precisely administered during specific periods of brain activity.

Groups of neurons in the brain continuously cycle in unison between periods of heightened and suppressed electrical activity called ‘oscillations’ or ‘rhythms.’ When the brain is awake, a cycling of neuronal activity called the ‘mu rhythm’ can be seen in brain regions that are responsible for sensory perception and movement, like the primary motor cortex. Dr. Leonardo Cohen, senior investigator at National Institute of Neurological Disorders and Stroke (NINDS), believes that studying this neuronal rhythm can potentially boost the effects of brain stimulation approaches like TMS, which uses magnetic fields to generate electrical currents in the brain.

The research team led by Dr. Cohen and Dr. Sara Hussain, a former postdoctoral fellow in his lab who is now an assistant professor at the University of Texas at Austin, explored whether delivering TMS during specific phases of neuronal oscillations could enhance learning in a study of 51 individuals practicing a repetitive motor skill task. All participants got better at the task as they practiced on the first and second days of the experiment, however, the participants who had received TMS stimulation only during trough phases of the brain’s mu rhythm improved nearly 50 percent more than the other groups.

“TMS stimulation for therapeutic purposes is usually given regardless of phase,” Dr. Cohen explains. “When we look at our results, we see that TMS during trough phases increases performance by nearly 50 percent, so in reality what researchers are doing right now is a mix of that 50 percent boost when TMS is given during trough phases and the zero percent improvement when TMS is given during peak phases. The mix of those makes the overall size of the effect potentially much smaller.”

Through this research effort, Dr. Cohen hopes to learn how TMS can be more effectively to help patients with neurological problems due to strokes or dementia regain their ability to perform complex movements like walking or grasping objects.

NIH researchers identify how two people controlled HIV after stopping treatment

Researchers at the National Institute of Allergy and Infectious Diseases (NIAID) have identified two methods that individuals with HIV can control the virus for an extended period after stopping antiretroviral therapy (ART) under medical supervision.

The study, led by Dr. Tae-Wook Chun, chief of the HIV Immunovirology Section in the Laboratory of Immunoregulation at NIAID and Dr. Anthony Fauci, NIAID director and chief of the Laboratory of Immunoregulation, involved two adults with HIV who began ART soon after acquiring the virus and continued with treatment to successfully suppress HIV for more than six years. The individuals discontinued ART under a medically supervised HIV clinical trial.

The study team monitored the timing and size of viral rebounds in each participant, that is, times when the amount of HIV in their blood became detectable. One participant suppressed the virus with intermittent rebounds for nearly 3.5 years, at which point he began taking suboptimal ART without informing the study team. The other participant almost completely suppressed HIV for nearly four years, at which point the virus rebounded dramatically because he became infected with a different HIV strain, a phenomenon known as “superinfection.”

The first participant had high levels of HIV-specific immune cells called CD8+ T cells that can kill virus-infected cells while the second participant did not, indicating that different mechanisms of control were at work in each person. The second participant, who had a weaker CD8+ T cell response against HIV, had a very strong neutralizing antibody response throughout the follow-up period until the sudden viral rebound. The scientists hypothesized that neutralizing antibodies may have played a significant role in facilitating near-complete HIV suppression in this individual until he acquired a different strain of the virus. The finding of this study could inform efforts to develop new methods of helping people with HIV put the virus into remission without taking lifelong medication, which can have long-term side-effects.

Buprenorphine misuse decreased among U.S. adults with opioid use disorder from 2015-2019

Buprenorphine is an FDA-approved medication used in the treatment of opioid use disorder and for the relief of severe pain. When used to treat opioid use disorder, buprenorphine works through the partial activation of opioid receptors in the brain, which aids in the reduction of opioid cravings, withdrawal, and overall use of other opioids.

In the National Survey on Drug Use and Health Data, conducted by the National Institute on Drug Abuse (NIDA) and the Centers for Disease Control and Prevention (CDC), nearly three-fourths of adults reporting buprenorphine use in 2019 did not misuse the medication in the past 12 months. Buprenorphine misuse among people with opioid use disorder has been trending downward between 2015-2019, despite increases in the number of people receiving buprenorphine treatment.

In 2020, more than 69,000 people lost their lives due to opioid related drug overdoses. However, in 2019, less than 18% of people with a past-year opioid use disorder received medications to treat their addiction, in part due to stigma and barriers to accessing these medications. Updated guidelines released by the U.S. Department of Health and Human Services in April 2021 has expanded access to buprenorphine for the treatment of opioid use disorder. However, barriers to the use of this treatment remain, including provider unease with managing patients with opioid use disorder, lack of adequate insurance reimbursement, and concerns about risks for diversion, misuse, and overdose.

The study reported roughly 1.7 million people having used buprenorphine as prescribed in the past year, compared with 700,000 people who reported misusing the medication. The study also concluded that people who did not receive treatment for their drug use and those living in rural areas were more likely to misuse the medication, however, being a racial/ethnic minority or living in poverty had no effect on buprenorphine misuse.

“Three-quarters of adults taking buprenorphine do not misuse the drug,” said Dr. Wilson Compton, Deputy Director of NIDA and senior author of the study. “Many people with opioid use disorder want help, and as clinicians, we must treat their illness. The study authors recommended that improvements to the access and quality of buprenorphine treatment for people with opioid use disorder is needed to address the current opioid crisis.

Wearable tech tracks ebbs and flows of bipolar disorder

Bipolar disorder is a mental health condition characterized by alternating periods of extreme elation or depression. This unpredictable change in moods and behavior are severe enough to interfere with work, school, and relationships for nearly 90 percent of people affected with bipolar disorder. While as many as 2.3 million Americans have been diagnosed bipolar disorder, it is likely many more people go undiagnosed.

Researchers at the National Institute of Mental Health (NIMH) are transforming our knowledge of bipolar disorder. In a study led by NIH Distinguished Investigator, Dr. Kathleen Merikangas, wearable activity monitors allowed a team of researchers to investigate how sleep and movement affect the moods of people with bipolar disorder and other mood disorders.

“When we studied adolescents in the general population, we learned that one of the most important characteristics of youth who begin to develop bipolar disorder is increased physical activity and energy rather than changes in mood,” explains Dr. Merikangas. In fact, physical activity has now been included as one of the core features in the diagnosis of bipolar disorder. People with this condition are fidgety, restless and moving around a lot even in situations where they would normally sit still.

To further understand the relationships between physical activity, sleep, and mood in patients with bipolar disorder in real-world settings, the research team studied 242 adults with bipolar disorder, major depression, or no history of mood disorders. The study participants wore monitors on their wrists that collected constant, real-time measurements of their activity and sleep duration for two weeks and were given electronic devices programmed with a survey that asked them several times per day to rate their mood and energy level on a scale from one to seven.

The researchers found that participants reported better moods on the survey when they had been more active earlier in the day. A lack of sleep correlated to reduced energy and activity, whereas changes in mood had no impact on energy levels. The influence of sleep and activity on the moods of bipolar participants was much stronger than in those with depression or no mood disorder, and the sleep- and movement-induced boosts in mood and energy level that they experienced took longer to return to more typical levels. As a result of these findings, Dr. Merikangas suggests that increasing physical activity may show promise in the treatment of bipolar disorder.

COVID vaccine booster increases antibody responses, is protective in rhesus macaques

A collaborative research team from Emory University, Bioqual, Moderna, and Johns Hopkins University, led by scientists at the National Institute of Allergy and Infectious Diseases Vaccine Research Center determined that a booster dose of the mRNA-1273 COVID-19 vaccine given to rhesus macaques about six months after their primary vaccine series significantly increased levels of neutralizing antibodies against all known SARS-CoV-2 variants of concern.

This study was conducted six months ago during a time in which the SARS-CoV-2 Beta variant was a major concern. The Beta variant has consistently shown the greatest ability to resist neutralization, likely reducing vaccine effectiveness. While Delta has become the dominant virus variant in the United States due to its high transmissibility, it only has a moderate ability to resist neutralization.

The researchers observed that increased neutralizing antibody responses were sustained for at least eight weeks after the boost. They also generated a higher level of protection by limiting virus replication in the lungs and nose, than after the primary vaccine series. These data suggest that boosting triggers a strong immune memory response and potentially longer lasting immunity.

The researchers concluded that an mRNA-1273 booster vaccine may improve the duration and potency of protection against upper and lower airway infection by any of the circulating SARS-CoV-2 variants. They note that this would be especially important to maintain protection against severe disease and possibly limit mild infection and virus transmission. Their results of the study support vaccine boosting for the elderly, people with pre-existing health conditions, those at high-risk exposure, and those who responded poorly to primary vaccination.

Upcoming Events:

NIMH Workshop on Advancing Training in Suicide Prevention Clinical Care

Wednesday, November 3, 2021, 11:00 am to Monday, November 8, 2021, 4:00 pm (registration required)

2021 Synthetic Biology Consortium Meeting

Thursday, November 4, 2021, 11:00 am to Friday, November 5, 2021, 3:00 pm (registration required)

The Child Opportunity Index: Health Equity Applications

Thursday, November 4, 2021, 2:00 pm to 3:30 pm

10th Annual David Derse Memorial Lecture and Award

Tuesday, November 16, 2021, 1:30 pm to 3:00 pm

NIH Rural Health Day Seminar

Thursday, November 18, 2021, 11:00 am to 5:30 pm (registration required)

NIH Behavioral and Social Sciences Research Festival

Thursday, November 18, 2021, 1:00 pm to Friday, November 19, 2021, 4:30 pm (registration required)

Cancer-related Emergency and Urgent Care: Prevention, Management, and Care Coordination

Wednesday, December 1, 2021 to Friday, December 3, 2021 (registration required)

NCI Symposium on Mutation Signatures and Cancer

Thursday, December 2, 2021 to Friday, December 3, 2021 (register by November 24)

The Meaning of Eugenics: Historical and Present-Day Discussions of Eugenics and Scientific Racism

Thursday, December 2, 2021, 10:00 am to Friday, December 3, 2021, 4:30 pm (registration required)

The post National Institutes of Health (NIH) Research Updates – November 2021 appeared first on Astrix.

Recent NIH Research

Infection hinders blood vessel repair following traumatic brain or cerebrovascular injuries

Traumatic brain injury, or TBI, occurs due to sudden external force to the brain resulting in damage to blood vessels and other internal tissue. Similarly, cerebrovascular injury (CVI) refers to a spectrum of injuries to the cervical carotid or vertebral arteries due to blunt force trauma. These conditions are a leading cause of long-term complications, disability or death depending on the severity of injury.

In a recent study, scientists from the National Institute of Neurological Disorders and Stroke (NINDS) have found that systemic infection, which often accompanies these types of conditions can negatively impact recovery and worsen outcomes. The research team, led by Dr. Dorian McGavern, discovered that viral, fungal, or a mimic for bacterial infections all impacted blood vessel repair within the meninges, the protective covering of the brain. Using a mouse model previously developed by the team for studying mild TBI (mTBI), they observed that some cells of the immune system no longer moved into the site of TBI injury, which occurred in the uninfected animals, suggesting they were responding to systemic infection. Similar findings were confirmed for CVI injury.

“Evolution prioritizes mobilizing the immune system to fight off infection over repair,” said Dr. McGavern. “Because the body is dealing with a greater threat, cells that would normally repair the damaged blood vessels in or around the brain are needed elsewhere.”

The infected mice were eventually able to repair the blood vessel damage at a later time unless a second infection was encountered. This timing is especially critical in the case of CVI mice, because the delay in response produced by infection led to permanent cognitive dysfunction and damage to the brain tissue.

Although the presence of infection was affecting the immune system’s ability to respond to mTBI, the exact cause remained unknown. The researchers observed that when cells in the body become infected, they release proteins that signal the immune system for help. One group of proteins released after viral infection are called type I interferons (IFN-I), which activate a variety of genes that affect the immune response. Following mTBI, the researchers saw a large increase in IFN-I-related genes in infected compared to non-infected mice. Additional experiments confirmed the role of IFN-I in shifting the focus of the immune system away from blood vessel repair.

Systemic infections are common among patients hospitalized for TBI and CVI, and have been linked to poorer outcomes. This study highlights the importance of controlling both bacterial and viral infections as quickly as possible, as a delay in repair can lead to permanent damage to the brain.

NIAID scientists find a key to Hepatitis C entry into cells

Hepatitis C is one of the most common bloodborne diseases in the United States. It is caused by the hepatitis C virus (HCV) from contact with infected blood. While the disease may be asymptomatic in its early stages, left untreated it can lead to severe liver damage, cancer and death. Currently, there is no vaccine to protect against HCV infection. Common routes of transmission are through exposure from unsafe injection practices such as intravenous drug use, unsafe healthcare or unscreened blood transfusions.

The Center for Disease Control reports that an estimated 2.4 million Americans are living with hepatitis C. More than half of all people infected with HCV are thought to develop a chronic infection. Effective antiviral medications are available to treat HCV infection for patients meeting the clinical criteria, however they will not prevent reinfection.

A team of researchers from the National Institute of Allergy and Infectious Diseases (NIAID) and colleagues examined the interaction between a protein expressed on the surface of the HCV, known as HCV E2, and a receptor called CD81 found on the surface of some human cells. Prior research had shown that antibodies interfered with interactions between these two proteins. This suggested that the interaction between HCV E2 and CD81 allowed HCV to enter and infect human cells. However, the exact mechanism of how this occurred was largely unknown.

In their new study, the team determined the exact structure of HCV E2 and CD81 and noted how the two proteins interacted when exposed to each other under different conditions. They found that under acidic conditions, HCV E2 easily binds to the CD81 receptor. Once the interaction between virus and receptor begins, HCV E2 changes shape, facilitating its entrance into the cell by putting the virus in closer contact with the cell membrane.

This ground-breaking research may provide the foundation for a vaccine against HCV that potentially could cause a person to make specific antibodies that prevent HCV E2 from binding with CD81, stopping the virus from entering the cell, and  thereby preventing HCV infection.

NINDS scientists build cellular map of multiple sclerosis lesions

Multiple Sclerosis (MS) is a chronic disease affecting the central nervous system, in which the immune system attacks myelin, the protective sheath surrounding nerve fibers. This causes inflammation and lesions that make it difficult for the brain to transmit signal to rest of the body. Chronic active plaques or lesions with inflamed rims have been linked to progressive MS, a more aggressive and disabling form of the disease. There is no cure for MS, and no therapies that directly treat chronic active lesions.

Scientists at the National Institute of Neurological Disorders and Stroke (NINDS) have constructed a cellular map of chronic MS lesions through the identification of the genes that play a vital role in the repair of lesions. This map, or ‘blueprint’ may reveal potential therapeutic targets for progressive MS.

“We identified a set of cells that appear to be driving some of the chronic inflammation seen in progressive MS,” said Dr. Daniel Reich, senior investigator at NINDS. “These results give us a way to test new therapies that might speed up the brain’s healing process and prevent brain damage that occurs over time.”

Chronic active lesions are characterized by a slowly expanding rim of immune cells called microglia, which normally help protect the brain. In MS, they can become overactive and secrete toxic molecules that damage nerve cells. Astrocytes and lymphocytes found near the lesions may also contribute to ongoing tissue damage, however, prior research suggests that microglia are primarily responsible for lesion expansion.

To gain a better understanding of the MS lesions, Dr. Reich’s team used single-cell RNA sequencing to analyze the gene activity profiles of more than 66,000 human brain tissue cells, post-mortem from MS patients along with healthy controls. The team found a large diversity of cell types in the tissue surrounding chronic active lesions compared to normal tissue, and a high proportion of immune cells and astrocytes at the active edges of those lesions. Microglia comprised 25% of all immune cells present at the lesion edges.

Further analysis revealed that the gene for complement component 1q (C1q), an important and evolutionarily ancient protein of the immune system, was expressed mainly by a subgroup of microglia responsible for driving inflammation, suggesting that it may contribute to lesion progression. According to the authors, it’s possible that targeting C1q in human microglia could halt MS lesions and related neurodegenerative diseases in their tracks and supports the use of chronically inflamed rim lesions as an MRI biomarker for disease progression.

NIDA study finds Methamphetamine-involved overdose deaths nearly tripled between 2015 to 2019

In a new study by the National Institute on Drug Abuse (NIDA), researchers have found that methamphetamine related overdose deaths among people ages 18-64 from 2015 to 2019 in the United States. The number of people who reported using methamphetamine during this time did not increase as steeply, but the analysis found that populations with methamphetamine use disorder have become more diverse. Increases in higher-risk patterns of methamphetamine use, such as methamphetamine use disorder, frequent use, and combined drug use, may be contributing to the rise in overdose deaths.

“We are in the midst of an overdose crisis in the United States, and this tragic trajectory goes far beyond an opioid epidemic. In addition to heroin, methamphetamine and cocaine are becoming more dangerous due to contamination with highly potent fentanyl, and increases in higher risk use patterns such as multiple substance use and regular use,” said Dr. Nora Volkow, NIDA Director and one of the authors of the study. “Public health approaches must be tailored to address methamphetamine use across the diverse communities at risk, and particularly for American Indian and Alaska Native communities, who have the highest risk for methamphetamine misuse and are too often underserved.”

The CDC reported an unprecedented 30% increase in overdose deaths in 2020 in the US, primarily driven by fentanyl and other synthetic opioids. Overdose deaths involving psychostimulants, and particularly methamphetamine, have also risen steeply in recent years, and many of these deaths involved use of an opioid at the same time. However, questions remain on how trends in methamphetamine use contribute to greater risk for overdose deaths.

The researchers found that from 2015 to 2019, the number of overdose deaths involving psychostimulant drugs other than cocaine, (largely methamphetamine), rose from 5,526 to 15,489, a 180% increase. However, the number of people who reported using methamphetamine only increased by 43% over the same period, indicating that riskier use patterns may have contributed to the increased numbers of methamphetamine-involved overdose deaths during this time period.

The team also noted significant shifts in the populations using methamphetamine between 2015 and 2019. Historically, methamphetamine has been most commonly used by middle-aged white persons. In this new study, it was determined that American Indians and Alaskan Natives had the highest prevalence of methamphetamine use, as well as methamphetamine use disorder and methamphetamine injection. Previous studies have found that American Indians and Alaskan Natives also had the largest increases in methamphetamine overdose deaths in recent years.

The study also determined the prevalence of methamphetamine use disorder among those who did not inject the drug increased 10-fold among Black people from 2015 to 2019, a much steeper increase than among white or Hispanic people. Methamphetamine use disorder without injection quadrupled in young adults ages 18 to 23, a substantially greater increase than in older age groups. This is of particular concern, as young adulthood is a critical period of continued brain, social, and academic maturation, and could have long-lasting consequences from methamphetamine use disorder during this vulnerable period.

Currently, there are no approved medications for the treatment of methamphetamine use disorder. The research team at NIDA is working to develop safe and effective medications aimed at slowing this sharp increase in methamphetamine use, overdoses, and related deaths.

NIH study provides insights into the origins of lung cancer in never smokers

A recent collaborative international study, led by scientists at the National Cancer Institute (NCI) has provided insights that will help unlock the mystery of how lung cancer arises in people who have no history of smoking and may guide the development of more precise clinical treatments.

A genomic analysis of lung cancer in people with no prior history of smoking has found that the majority of these tumors arise from the accumulation of mutations caused by natural processes in the body. It describes for the first time three molecular subtypes of lung cancer in people who have never smoked.

“What we’re seeing is that there are different subtypes of lung cancer in never smokers that have distinct molecular characteristics and evolutionary processes,” says Dr. Maria Teresa Landi, senior investigator at NCI’s Integrative Tumor Epidemiology Branch and study leader. “In the future we may be able to have different treatments based on these subtypes.”

The research team is starting to distinguish subtypes that could potentially have different approaches for prevention and treatment. Dr. Landi noted that a slow-growing piano subtype could give clinicians a window of opportunity to detect these tumors earlier when they are less difficult to treat. The mezzo-forte and forte subtypes have only a few major driver mutations which could enable tumors to be identified by a single biopsy and could benefit from targeted treatments.

Lung cancer is the leading cause of cancer-related deaths worldwide, with a global estimate of more than 2 million people annually diagnosed with the disease. Most people who develop lung cancer have a history of tobacco smoking, however, between 10% and 20% of people who develop lung cancer have never smoked. Lung cancer in never smokers occurs more frequently in women and at an earlier age than lung cancer in smokers. Environmental risk factors, such as exposure to secondhand tobacco smoke, radon, air pollution, and asbestos, or prior lung diseases, may explain some lung cancers among never smokers, but scientists still are not certain what causes the majority of these cancers.

Upcoming Events

Advancing NIH Research on the Health of Women

Wednesday, October 20, 2021, 8:30 am to 5:00 pm (registration required)

Macrophage Infection by HIV: Implications for Pathogenesis and Cure

Wednesday, October 13, 2021 to Thursday, October 14, 2021 (registration required)

NIH Behavioral and Social Sciences Research Festival

Friday, November 19, 2021, 9:00 am to 5:00 pm

The post National Institutes of Health (NIH) Research Updates – October 2021 appeared first on Astrix.

Recent NIH Research

Experimental Compound Supercharges Cellular Power Plants

In a recent IRP study, researchers have identified a novel therapeutic strategy that could aid in treating obesity and related metabolic diseases, such as heart disease and diabetes, through increased cellular energy production. Mitochondria, first coined the “the powerhouse of the cell” by Philip Siekevitz in 1957, provides most of our cells’ supply of energy in the form of adenosine triphosphate (ATP). The regulation of the synthesis and degradation of ATP to ADP is carried out by AMPK (5′ AMP-activated protein kinase), an enzyme that is activated when cellular energy supplies are low. This master regulator protein increases mitochondrial energy production during times of metabolic stress such as low carbohydrate levels. To further reach a state of cellular homeostasis, AMPK elevates mitophagy activity, which acts as a quality control mechanism that degrades mitochondria that are damaged or no longer required.

Why mitochondrial dysfunction occurs, less energy is being produced and reactive oxygen species (ROS) are created that cause cellular damage. This is a serious concern particularly in individuals with obesity. Since AMPK only ramps up mitophagy when energy is scarce, their abundant stores of energy in the form of body fat and excess glycogen, a form of sugar, depress AMPK activity.

“One of the problems that occurs with obesity is, because there’s such a surplus of energy, mitochondria production, as well as quality control, declines because you don’t need those energy factories to be working very efficiently or very hard,” says Dr. Jay Chung, senior investigator at the NHLBI’s Laboratory of Obesity and Aging Research. “The cell pays less attention to mitochondria because it doesn’t need them as much, and when you neglect the quality control of mitochondria, you get an accumulation of damaged mitochondria, which can produce ROS and cause many of the diseases that stem from obesity: diabetes, heart disease, and so forth.”

The drugs that are currently in use for the treatment of those diseases through the direct activation of AMPK cause side effect that can pose serious health risks, such as the enlargement of the heart that can potentially lead to heart failure. Through a prior IRP study, Dr. Chung’s research team discovered an alternative route for the activation AMPK. They found that inhibiting an enzyme called PDE4 (Phosphodiesterase-4), caused an increase in AMPK and mitophagy activity, resulting in improved mitochondrial function, increased physical stamina, and blood sugar regulation in mice, providing protection from diet-induced obesity. Unlike other PDEs, PDE4 is not present in the heart, so drugs that target it should not cause the same heart problems as the direct AMPK activators.

To test this theory, Dr. Chung collaborated with a team of organic chemists to synthesize several brand-new molecules whose structures suggested they could inhibit PDE4. Subsequent tests revealed that one of these compounds, named CBU91, only inhibited PDE4 and not its close cousins, and it was also much more effective at inhibiting PDE4 than the drug Dr. Chung’s lab used in its prior study.

Using myotubes, collections of cells that closely resemble muscle fibers, the research team found that CBU91 increased AMPK and mitophagy activity, resulting in a greater ability for the treated cells to burn fat molecules for fuel. The CBU91 treated myotubes also had much higher levels of messenger RNA molecules, used to increase production of the PGC1-alpha protein, an enzyme that drives the production of new mitochondria. Due to the fact that AMPK activity increases when cells die, the researchers conducted tests to validate that the cells treated with CBU91 were not dying at a faster rate that the untreated cells.

The higher amount of healthy mitochondria that are present in cells, the greater the body’s ability to burn fat and regulate blood sugar, making drugs with effects like those of CBU91 extremely promising as treatments for obesity and diabetes. They may also have potential for treating Alzheimer’s disease as the buildup of dysfunctional mitochondria in neurons is present in that illness as well. In future studies, Dr. Chung plans to investigate which types of PDE4 are present in various bodily tissues and develop compounds that inhibit only specific forms of it to reduce potential side effects.

A Record-Breaking Sprint to Create a COVID-19 Vaccine

December 2019 marks the start of what would quickly become a global pandemic, with the first human cases of this “pneumonia-like” illness originating in Wuhan, China. By January 2020, Chinese scientists had isolated a new coronavirus, SARS-CoV-2, that was responsible for causing this serious epidemic. When the genetic sequence was released to the worldwide scientific community, viral immunologists, Dr. Barney Graham, director of the VRC’s Viral Pathogenesis Laboratory (VPL) and Dr. Kizzmekia Corbett, VRC research fellow, immediately began working on a vaccine for the illness that would become known as COVID-19.

“Dr. Corbett was directing a team doing coronavirus work, and we had relationships with three or four really good academic collaborators and had been having monthly conference calls for years,” Dr. Graham says. “We also had our industry collaborators, and we had a strategy and all the technology, so we were ready to go.”

Dr. Graham and Dr. Corbett quickly developed their plan of attack. The team went to work on designing an antigen, a copy of the spike protein found on the surface of the COVID-19 virus which it uses to infect cells. After years of prior work on coronaviruses, along with their partners at Moderna, the research team perfected a method to coax the body to manufacture antigens via messenger RNA (mRNA). Within 48 hours after the release of the coronavirus’ genome, the team had designed the protein that would be used for their candidate COVID-19 vaccine. The VRC then began clinical trials in collaboration with Moderna and clinical investigators from NIH’s Division of Microbiology and Infectious Diseases (DMID). Ultimately, the vaccine received emergency use authorization from the U.S. Food and Drug Administration (FDA) on December 18, 2020, just one week after a similar vaccine developed by Pfizer.

In recognition of this groundbreaking success in developing a life-saving COVID-19 vaccine in record time, Dr. Graham and Dr. Corbett were named finalists for the 2021 Samuel J. Heyman Service to America Medals, also known as the ‘Sammies.’ Often referred to as the ‘Oscars of government service,’ the Sammies honor exceptional work by government employees.

While creation of the specific vaccine for COVID-19 was surprisingly fast, Dr. Graham and Dr. Corbett, along with fellow researchers in their field, had been laying the groundwork for decades. In Dr. Graham’s prior studies on respiratory syncytial virus (RSV), a vaccine prepared from inactivated virus actually caused the disease to worsen in children who received it. Dr. Graham discovered that the original RSV vaccine induced a response from immune cells creating an allergic-type reaction, making a lot of mucus and not effectively clearing the virus from the body. Inactivating the virus also caused it to change shape to the form it takes once it has already infected and fused with a cell. As a result, the vaccine caused the body to release antibodies that could bind to the virus but could not block infection, making it ineffective. These findings provided the foundation for him to create vaccines that could emulate the pre-fusion form of the virus.

Dr. Graham continued the RSV project in 2000 when he was recruited to the NIH to help create the VRC. He and Dr. Jason McLellan, a postdoctoral fellow in the lab of IRP senior investigator Dr. Peter Kwong, isolated and created 3D models of the pre-fusion RSV virus protein. The resulting vaccine using the pre-fusion model of the virus enabled the body to produce antibodies that were 16 times more potent than the original vaccine. The discovery of the pre-fusion structure proved foundational to the work Dr. Graham’s lab subsequently began on coronaviruses such as SARS and MERS. “After we had the RSV breakthrough, Dr. McLellan and I decided that coronaviruses were similar enough to RSV and there was no structural information for them,” Dr. Graham says. “That was a good area to work in because it was a wide-open field and it needed to be done.”

In 2014, Dr. Corbett joined the VPL as a senior research fellow and focused her work on understanding the mechanism that antibodies use to bind to different forms of coronavirus spike proteins to block infection. She also began work on a method for quickly and reliably developing antigen proteins to match each virus and to deliver the instructions for making these proteins to cells via mRNA.

The VRC was already gearing up for clinical trials with Moderna to test an mRNA vaccine against Nipah virus, which the lab had developed in parallel with an mRNA vaccine against the coronavirus that caused the 2012 MERS outbreak. As a result, by the time COVID-19 emerged, the VPL was well positioned to switch gears to a vaccine for COVID-19 and hit the ground running.

With the race to develop a safe and effective COVID-19 vaccine winding down, both Dr. Graham and Dr. Corbett are planning their future endeavors. Dr. Graham hopes to retire at the end of the year and devote time to improving communication and education about science and technology, particularly in low- and middle-income countries. In June, Dr. Corbett left the NIH to lead her own laboratory at Harvard University’s T.H. Chan School of Public Health, where she plans to continue her work on coronaviruses. She is also working to educate the public about vaccination and addressing vaccine hesitancy, particularly in communities of color, and hopes to inspire young people to pursue careers in science.

Words Matter: Language can Reduce Mental Health and Addiction Stigma, NIH Leaders Say

People with mental illness and substance addiction have long been stigmatized throughout society arising from their inability to adhere to social norms. Public education, training of healthcare professionals, and advancements in medicine have aided in reducing the stigma surrounding these conditions but further efforts are needed. In a recent article published in Neuropsychopharmacology, NIH leaders discuss how using the appropriate language to describe mental illness and addiction helps to reduce stigma, thereby improving how individuals with these conditions are treated within the health care system and throughout society. The words we use can also impact the likelihood that these individuals will seek out treatment and of the quality of care that they may receive. Findings from over a decade of research concludes that stigma associated with mental illness or a substance abuse disorder can result in negative health outcomes and creates a barrier to seeking treatment.

Statistics show that nearly 35% of people in the US with serious mental illness conditions and approximately as high as 90% of people having substance abuse disorders, do not receive treatment for their conditions. The authors, Dr. Nora Volkow, NIDA Director, Dr. Joshua Gordon, NINDS Director, and Dr. George Koob, NIAAA Director, point to findings that suggest that stigma-related bias among clinicians is a contributing factor to a treatment-averse mindset and to suboptimal clinical care, including the failure to implement proven methods of treatment. When a person with a mental illness or substance abuse disorder continues to experience stigma, they may begin to internalize it. This “self-stigma” often leads to poor self-esteem, feelings of lower self-worth, and can become an ongoing source of distress that may exacerbate symptoms and create barriers to successful treatment.

Reducing the stigma that is often associated with these conditions will help to alleviate the psychological burden it places on the affected individuals, breaking down the barriers to receiving effective healthcare. The authors highlight numerous studies showing that using scientifically accurate language and terms that centralize the experience of patients with mental illness and substance abuse disorders is one of the primary components to reducing stigma. They recommend that a shift in language is of critical importance for mobilizing resources toward mental health and addiction services and reducing the prejudices that prevent people from seeking help or receiving the quality of services they need. While the quest to eliminate the stigma and prejudice associated with mental illness and addiction, the authors contend that changing the language we use to describe these conditions can make a significant and immediate difference for the people experiencing them.

Upcoming Events:

Relating Target Engagement to Clinical Benefit: Biomarkers for Brain Disorders of Aging

Wednesday, August 25, 2021, 1:00 pm to 5:00 pm

Science and Regulation of Bacteriophage Therapy

Monday, August 30, 2021, 9:30 am – 3:30 pm,  Tuesday, August 31 and Wednesday, September 1, 2021, 10:00 am – 3:00 pm

Food Insecurity, Neighborhood Food Environment, and Nutrition Health Disparities: State of the Science

Tuesday, September 21, 2021, 12:30 pm to Thursday, September 23, 2021, 5:30 pm (registration required)

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