# Director's Messages

- Highlights from the Annual NIH HEAL Initiative Scientific Meeting: Excellent Science and Collaboration Drive Pain Research Forward Highlights from the Annual NIH HEAL Initiative Scientific Meeting: Excellent Science and Collaboration Drive Pain Research Forwardduprekb@nih.govThu, 03/21/2024 - 18:52            Friday, March 22, 2024                  Pain affects more than 50 million Americans, with 25 million American adults reporting severe daily pain. An important pillar of NIH’s efforts to improve the treatment of pain is the Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative®, which seeks to find innovative scientific solutions to address the public health crises of opioid use disorder, overdose, and pain. The National Institute on Drug Abuse (NIDA) and NINDS jointly lead the HEAL Initiative, in close collaboration with other NIH Institutes, Centers, and Offices. Within HEAL, NINDS coordinates research efforts across NIH to develop safe and effective therapies for acute and chronic pain and improve pain management. You can read about our areas of progress and accomplishments across all research areas of the HEAL Initiative in the recent 2024 Annual HEAL Report. In February, NIH held the 5th Annual NIH HEAL Initiative Scientific Meeting. More than 800 researchers, NIH leadership and staff, people with lived experience, community partners, and other collaborators from across the country participated to share exciting research advances. I am happy to highlight some of the progress presented at the meeting on HEAL-supported pain research and invite you to watch the videos of the plenary sessions available on the HEAL website.  HEAL pain research spans the discovery and validation of novel targets for treating pain conditions to preclinical development and to clinical trials and implementation research to ensure that novel treatments can be incorporated into health care practice. I’m encouraged to see HEAL researchers developing novel models and screening tools for testing new medications. For example, the Preclinical Screening Platform for Pain (PSPP) has screened 40 assets for their potential to warrant further development as new therapies. In addition, the PRECISION Human Pain Network studies human tissues and cells to identify cell types, phenotypes, and underlying human pain and to accelerate the discovery and validation of innovative therapeutic targets. Meeting participants also described progress in HEAL-supported research on novel approaches to treat chronic pain, such as post-operative ketamine infusion to prevent persistent post-operative pain, as well as disease-modifying gene therapy and non-pharmacological therapies for chronic pain. One exciting advance is the successful use of closed loop recordings of brain activity with targeted deep brain stimulation (DBS) to alleviate chronic pain. This approach involves implanting electrodes in people with chronic pain to measure brain activity during pain, which then triggers stimulation of specific brain areas to dampen the pain-inducing signals. An individual who had experienced unrelenting, debilitating chronic pain for decades described how this tailored DBS treatment transformed his health and quality of life. After receiving the treatment in a HEAL-supported study, he has been able to resume working and playing music in a band. While his experience is a singular success, it is a powerful reminder of the importance of HEAL’s mission and the dedicated work of HEAL scientists in partnership with people who live with chronic pain. Many presentations about clinical pain management, including efforts to enhance equity-focused pain management, emphasized the need to consider individual and contextual factors in pain research and when diagnosing patients and choosing the best course of treatment. The HEAL Health Equities program for pain will develop culturally tailored pain management strategies for a diverse range of populations across many levels of health care settings from self-management programs to emergency rooms. My colleague, Dr. Lindsey Criswell, Director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, reiterated such a whole-person focus in a panel discussion with several other NIH institute directors. As Dr. Criswell pointed out, to understand and treat pain, we need not only to understand physiological drivers of pain but also the experience of the individual. Similarly, Dr. Helene Langevin, Director of the National Center for Complementary and Integrative Health, noted that we need to consider body, mind, behavior, and even social support systems when studying how pain resolves and how best to include them as part of effective treatment. The panelists emphasized that to be successful, this research requires collaboration, team science, integration of different kinds of research and data, and above all inclusion of people with lived experience at all stages of the research process.Beyond scientific presentations, the HEAL meeting also provided an opportunity to recognize investigators who have excelled in research and community engagement. In all, 21 investigators received NIH HEAL Initiative Awards for Excellence in Research, Mentorship, Interdisciplinary Collaboration, and Community Partnership, as well as Trailblazer Awards. You can read about these exceptional 2024 awardees on the HEAL website. I applaud these individuals who, through the work they do along with their colleagues, give hope to people living with chronic pain and/or opioid use disorder. HEAL is working on several fronts to strengthen and diversify the pain research workforce, including support of trainees and early-stage investigators to attend the annual meeting. The meeting provided a platform for these early-career investigators to network and exchange ideas with the HEAL scientific community and present their work during the scientific poster sessions. Hundreds of researchers also had the chance to connect with the PURPOSE (Positively Uniting Researchers of Pain to Opine, Synthesize, & Engage) Network, which aims to connect pain researchers across disciplines to promote collaborations on NIH-funded pain research and enhance their training experience. If you were unable to connect with the PURPOSE Network at the meeting, I encourage you to learn about it online and sign up to participate. Although the accomplishments shared at the HEAL meeting are not sufficient to solve the pain crisis, they are proof of what we can achieve when we come together, leave our silos, collaborate across fields, and value and incorporate the input of our communities and individuals with lived experience. By convening participants with widely varying expertise and perspectives, the meeting created a dynamic venue for discovering potential synergies and sparking new connections and collaborations that will yield fruitful results in coming years. Future directions for HEAL Initiative research were also a focus at the February meeting of the HEAL Multi-Disciplinary Working Group (MDWG). Dr. Nora Volkow, Director of NIDA, and I shared many thoughts about the evolution of the initiative and its structure and recognize the value of developing a strategic plan for HEAL’s future research directions. We aim to launch this effort soon and will provide opportunities for input on the development and content of the plan to our communities. Feedback from individuals in the trenches of research, healthcare practitioners, and affected individuals and communities is indispensable for HEAL as we work to continue impactful research advances, guided by collaborative efforts and a commitment to addressing the multifaceted challenges of pain. We look forward to hearing from you in the future.  
- Brain Awareness Week 2024: Exciting curiosity about the brain and careers in brain science Brain Awareness Week 2024: Exciting curiosity about the brain and careers in brain sciencereidtn@nih.govTue, 03/12/2024 - 15:23            Wednesday, March 13, 2024                  NINDS is excited to participate in Brain Awareness Week during March 11-17. This week-long celebration of the marvels of the human brain began in 1996, established and still coordinated by the Dana Foundation, a private philanthropic organization that works to advance neuroscience research that benefits society. Today, Brain Awareness Week offers opportunities for brain scientists and enthusiasts around the world to bring their knowledge and passion to the public and communicate about the progress and promise of brain research.  Anyone wishing to share their knowledge and enthusiasm for the brain can host Brain Awareness Week activities, and all are welcome to attend and participate. The Dana Foundation provides resources to help in developing and promoting activities for a range of audiences, both in person and virtually. Follow the hashtags #BrainAwarenessWeek and #BrainWeek on social media and locate a science center near you to find activities to join in your community.NINDS has been proud to join Brain Awareness Week for over a decade to impart our love of brain science, inspire the next generation of brain scientists, and enhance public awareness about the brain. This year, I am happy to let you know that we will continue our partnership with the National Museum of Health and Medicine in Silver Spring, Maryland at their Brain Awareness Day celebration on March 16, a free community event that brings together medical professionals and brain researchers to provide hands-on learning about the brain, brain injury, and careers in brain science. We will also share virtual Brain Awareness Week activities on social media, including videos quizzing you about brain facts, testing your knowledge on brain truths and myths, and demystifying traumatic brain injury research. You can find even more videos and brain science activities for all ages on our NINDS Brain Educational Resources page.Although Brain Awareness Week is a prominent time to disseminate information about the brain in fun and creative ways, NINDS promotes online and in-person neuroscience education and outreach activities throughout the year. NINDS has developed additional partnerships with local organizations to bring neuroscience into the communities surrounding the NIH campus. Since 2015, the Prince George’s County (Maryland) Memorial Library System has invited NINDS to summer and after school events where students take part in imaginative activities lead by NINDS staff volunteers to encourage students’ curiosity about the brain and learn about paths to careers in science. In addition, our passionate volunteers have brought the NINDS Lobe-oratorium to community events since 2019, such as Scout Day at the National Museum of Health and Medicine. This exhibit uses colorful graphics and real-world examples to tell the story of the lobes of the brain and how the brain allows our bodies and minds to do all the amazing things they do every day! This April, the Lobe-oratorium will travel to Rockville Science Day, hosted by the Rockville Science Center, where more than 3,000 visitors will learn the fascinating functions of their brain from NINDS scientists and research staff. I am grateful to our volunteers who demonstrate that science is for everyone while inspiring students to explore their curiosity about the brain and careers in brain science.              Image                              Scouts ask NINDS volunteers their most burning questions about the brain and take home goodie-bags filled with our learning materials for kids and adults.              Image                              A young scout talks with volunteers about the brain.              Image                              The NINDS Lobe-oratorium on display.One of the goals of NINDS outreach is to inspire young people to learn about the brain and careers in brain research, and we hope these efforts also can help to broaden the diversity of the neuroscience workforce. By engaging in outreach efforts throughout the year, volunteers from NINDS’ talented workforce showcase the diversity of scientists and STEM professionals who are essential to the everyday processes of brain research, while bringing fun science to the public. A new endeavor called the NINDS Diverse Pathways to Science Video Series spotlights NINDS scientists, the many different paths they have taken, and the challenges they have overcome along their science journeys. The first scientist featured in this series is Dr. Lataisia Jones, NINDS Scientific Review Officer, who is also known to her many students as “Dr. Tay.” She described her journey, from childhood dreams of becoming a basketball player to thrilling neuroscience research experiences that led to her success as the first African American to receive a Ph.D. in the Department of Biomedical Sciences at Florida State University.                              Visit the NINDS Diverse Pathways to Science Video Series for more videos in this series.You can stay up-to-date on Brain Awareness Week and other events as well as scientific advances by following us on Facebook, X, and LinkedIn. For learning resources from across the NIH’s 27 institutes and centers including games, virtual laboratories, printable activity books, and videos, check out the NIH STEM Teaching Resources page.You can also use the NINDS Health Information page to learn about more than 400 brain disorders and find out how you can participate in research at ClinicalTrials.gov. For updates on advances in brain technologies research, you can subscribe to The BRAIN Blog from the NIH BRAIN Initiative, including updates from NIH BRAIN Director, Dr. John Ngai.I welcome you all to take part in Brain Awareness Week through our in-person and virtual activities and in your local communities this week and throughout the year.
- Highlights from February 2024 National Advisory Neurological Disorders and Stroke Council Meeting Highlights from February 2024 National Advisory Neurological Disorders and Stroke Council Meetingreidtn@nih.govMon, 02/26/2024 - 13:00            Tuesday, February 27, 2024                  The National Advisory Neurological Disorders and Stroke (NANDS) Council met virtually from February 14-15, 2024. The NANDS Council is composed of highly accomplished scientists and clinicians as well as members of the public, such as representatives from patient groups. Together, these Council members bring broad expertise and experience to guide NINDS on program planning, policies, and research priorities. They also provide a second level of review for all grants and cooperative agreements that NINDS is considering for funding and review ongoing programs in both the extramural and intramural research programs. I am grateful to them for giving their time and expertise to the NIH. I’d also like to thank Dr. David Owens, who is serving as Acting Director of the Division of Extramural Research at NINDS, and Dr. Anna Taylor, serving as Acting Deputy Director of the Division of Extramural Research, for their work to run this Council meeting.In my Director’s Report to Council, I discussed how NINDS is responding to an uncertain budget for the remainder of the current fiscal year and beyond. These challenges come in the context of increasing costs to conduct research, with the average requested cost for grant applications and the number of applications to NINDS both rising in recent years. We continue to plan for a number of possible budget scenarios, and NINDS staff are working hard to make the most of taxpayers’ investment in neuroscience research. I also shared updates on our activities with NANDS Council working groups, including our implementation of the Fundamental Neuroscience Working Group Recommendations and the new IdeaScale campaign launched by the NANDS ME/CFS Research Roadmap Working Group. In addition, I discussed several NIH-wide policy updates, including reports from two working groups of the Advisory Committee to the NIH Director: Re-envisioning NIH-Supported Postdoctoral Training and Catalyzing the Development and Use of Novel Alternative Methods to Advance Biomedical Research.The Brain Research Through Advancing Innovative Neurotechnologies® Initiative, or The BRAIN Initiative®, is celebrating its 10th year of supporting ground-breaking science, and I took some time to highlight its remarkable accomplishments. Last year, a research team based at the University of Pittsburgh published a study demonstrating spinal cord stimulation improving voluntary arm and hand movement in two people with partial paralysis after a stroke. Remarkable results have been reported with similar spinal stimulation in persons with spinal cord injury and Parkinson’s disease. As a neurologist, I am heartened to see the recent development of such promising applications. Additionally, the BRAIN Initiative Cell Census Network (BICCN) completed several momentous projects last year, reported in a landmark compendium of over 20 papers detailing the cell types of human and non-human primate brains, and a series of 10 papers describing the type, location, and molecular information of more than 32 million cells in the mouse brain. These extraordinary efforts will propel the field of neuroscience forward by enabling precise access to different cell types to monitor and modulate the activity of neural circuits.We also heard from Dr. Helene Langevin, Director of the National Center for Complementary and Integrative Health, who presented on two current challenges in research on musculoskeletal pain: First, connecting our extensive knowledge of the neuro-psycho-social aspects of musculoskeletal pain with the less-studied peripheral tissue environment of musculoskeletal pain beyond the nervous system (structural, mechanical, and metabolic); Second, understanding and supporting the various ways that our central nervous system reduces and augments perceptions of pain (also known as endogenous pain resolution) and the prevention of acute to chronic musculoskeletal pain transition. Dr. Langevin highlighted several bold and ambitious programs through the NIH Helping to End Addiction Long-term® (HEAL) Initiative that are addressing these challenges, including Developing Quantitative Imaging and Other Relevant Biomarkers of Myofascial Tissues for Clinical Pain Management, the Restoring Joint Health Function to Reduce Pain Consortium (RE-JOIN), and the Back Pain Consortium Research Program (BACPAC). Putting all of these projects together, we hope to obtain a more complete picture of musculoskeletal pain. We learned more about NIH HEAL Initiative preclinical programs from Dr. Michael Oshinsky, Director of the NINDS Preclinical Pain Office. Dr. Linda Porter, Director of the NINDS Office of Pain Policy and Planning, provided an update on the overall HEAL Initiative pain portfolio, including clinical and workforce programs. You can read more about the crucial work of the HEAL Initiative in my September 2023 Director’s Message and an upcoming message, so stay tuned!The open session of the meeting also included initiatives for concept clearance, including a new concept for institutional research training programs in neurological health disparities/health equity research (approved concepts will be posted in coming weeks), and an update on the NINDS Intramural Research Program (IRP) from Dr. Jeffery Diamond, the Scientific Director. The NINDS IRP is home to more than 500 scientists who conduct leading-edge basic, translational, and clinical research in neuroscience, neurology, and neurosurgery at NINDS laboratories in Bethesda, Maryland. The NINDS IRP has a robust cohort of investigators at early, mid, and late career stages making scientific advances in areas such as epilepsy, dementia, stroke, and amyotrophic lateral sclerosis. I highlighted many of these advances from the NINDS IRP, along with others funded by the NINDS Extramural Research Program, in my January 2024 Director’s Message.Finally, Alissa Gallagher, Director of the NINDS Office of Neuroscience Communications and Engagement, led a discussion about our plan to use the upcoming 75th Anniversary of NINDS to communicate and celebrate our scientific accomplishments, imagine the future of neuroscience, broaden our networks of collaboration, and help to restore public trust in science. As part of this celebration, we will travel across the country and convene scientific symposia and workshops to help broaden the reach and impact of our scientific progress and to foster our critical working relationships with you and all of our partners by engaging in bi-directional communications. These anniversary activities will also be timely opportunities to engage with our community as we set the stage for the next NINDS Strategic Plan. We look forward to celebrating this important milestone with all of you. Please be on the look-out as we share more information and opportunities for public engagement over the next year.I am incredibly grateful to our program, grants management, committee management, and all staff at the Institute who contribute to making these Council meetings a success.Related Resources:NANDS Council 222nd Meeting Agenda(pdf, 187 KB)	NIH Videocast of the 222nd meeting of the NANDS Council (timestamps included below)	Report of the Interim Director, Division of Extramural Activities, NINDS [05:42-18:54]		Report of the Director, NINDS, and Discussion [18:58-1:18:03]		Multi-IC Program on Musculoskeletal Pain [1:18:44-1:56:45]		HEAL Initiative Update and Council Discussion [1:56:46-2:54:12]		Concept Clearance [2:54:13-3:25:50]		75th Anniversary Discussion [3:25:51-3:43:00]		State of Intramural Research Program [3:43:01-4:07:45]
- Reflecting on 2023: Supporting Neuroscience in Service of Our Mission Reflecting on 2023: Supporting Neuroscience in Service of Our Missionhsuns@nih.govMon, 01/08/2024 - 10:34            Tuesday, January 9, 2024                                                                      NIH BRAIN Initiative Cell Census Network (BICCN): The first complete cell census and atlas of a mammalian brain and a quest toward defining the human brainThe BRAIN Initiative - Cell Census Network (BICCN) is a consortium of centers in the United States and Europe that work cooperatively to characterize the vast multitude of brain cell types and functions. After five years of extensive work funded by The Brain Initiative®, the BICCN produced an atlas, published in a collection of 10 papers in the journal Nature, that describes the type, location, and identity of more than 32 million cells in the mouse brain. The atlas also delineates the neurotransmitters and neuropeptides used by different cells and the relationship among cell types. This information creates a detailed blueprint for how chemical signals are initiated and transmitted in different parts of the brain. In a parallel effort, published in 21 papers across Science, Science Advances, and Science Translational Medicine, the BICCN compared over 3 million cells across human, nonhuman primate, and rodent brains across developmental periods. This triumph of team science has helped reveal what makes us uniquely human and sets the stage for the BRAIN Initiative Cell Atlas Network which hopes to generate a complete reference atlas of cells in the human brain across development.Image: A circular "mandala" type diagram that starts with a whole mouse brain in the center and expands out to multi-colored cell-type clusters. The circle is bordered by multicolored coronal and sagittal flat brain sections where the colors represent different types of RNA.Articles:BICCN: The first complete cell census and atlas of a mammalian brainScience: A quest into the human brainNIH Press Release(s):Scientists Unveil Complete Cell Map of a Whole Mammalian Brain                                                             Epidural stimulation of the cervical spinal cord for post-stroke upper-limb paresisGlobally, one in four people over the age of 25 will suffer from a stroke. Nearly three-quarters of these individuals exhibit lasting deficits in motor control of their arm and hand. In this study, funded by the National Institutes of Health’s Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative and published in Nature Medicine, spinal cord stimulation of the cervical sensory nerve roots was able to restore motor function in two stroke patients without any adverse issues. Researchers provided continuous stimulation through two linear implants, which amplified the connection between patients’ cortex and cervical spinal circuits. This improved strength, range of motion, function of the arm and hand, and allowed patients to perform complex tasks, like eating with utensils. By the end of the study, these benefits persisted even when stimulation was turned off. While this study was limited in scope, it demonstrates an exciting avenue for future therapeutic device development.Image: A cartoon representation of a the research setup, showing an individual performing a reaching task. The image depicts the site of stroke in the brain, wireless EMG sensors on the arm and forearm, a depiction of an external stimulator, and an indicator of where leads were implanted. To the upper right is an enlarged image depicting the anatomy of the cervical and thoracic spinal column that depicts the area where each electrode made contact.Articles:Powell M et al. Epidural stimulation of the cervical spinal cord for post-stroke upper-limb paresis. Nature Medicine. February 20th, 2023NIH Press Release: Study finds spinal cord stimulation may restore arm and hand mobility after stroke                                                             First-in-human prediction of chronic pain state using intracranial neural biomarkers Chronic neuropathic pain syndromes such as post-stroke and phantom limb pain are often resistant to treatment. This type of pain has been measured through subjective self-report, which limits how well data can be compared across individuals. In this study, funded by The BRAIN Initiative® and the NIH HEAL Initiative® and published in Nature Neuroscience, researchers implanted electrodes in four people with chronic neuropathic pain to record neural activity in two brain regions thought to integrate sensory, emotional, and cognitive dimensions of pain: the anterior cingulate cortex (ACC) and the orbitofrontal cortex (OFC). By allowing patients to initiate recordings multiple times a day over months and using machine learning to interpret the data, researchers were able to identify neural signals that worked as objective markers of pain. They were also able to differentiate these signals from those caused by acute pain in the same patients. These tools are a leap forward in developing novel methods for tracking and treating chronic pain.Image: Left: An x-ray showing where electrode leads are placed in the brain and where the recording device was implanted near the shoulders. Right, top: A representation of a frontal view of the brain where the ACC is colored in blue, the OFC is colored in yellow, and red dots show where electrode leads were placed. Right, bottom: A side view of the brain with the same color-scheme. Below it are lines that are raw recorded data from the implanted electrodes. The ACC line is blue and the OFC line is yellow.Articles:Shirvalkar P et al. First-in-human prediction of chronic pain state using intracranial neural biomarkers. Nature Neuroscience. May 22nd, 2023.NIH Press Release(s):Brain signatures for chronic pain identified in a small group of individualsBrain activity predicts chronic pain                                                             Deep Phenotyping of Neurologic Post-Acute Sequelae of SARS-CoV-2 InfectionDr. Mina and colleagues aimed to comprehensively characterize the poorly understood neuro-PASC features linked to SARS-CoV-2 infection. Participants were evaluated at a median of 9-months post-COVID-19 and compared with healthy volunteers. The main findings include the persistence of cognitive difficulties and fatigue, highly disabling conditions, and smell dysfunction. Brain MRI scans were mostly normal. Cerebrospinal fluid analysis identified intrathecal oligoclonal bands in three cases. Participants showed abnormalities in both CD4+ and CD8+ T cells, alongside increased frequencies of antibody-secreting B cells and cells expressing immune checkpoint molecules. Taken together, the findings add to growing evidence that widespread immunological and autonomic nervous system changes may contribute to Long COVID. The results may help researchers better characterize the condition and explore possible therapeutic strategies, such as immunotherapy.Image: Symptoms of neuro-PASC; bars on the right represent the frequency of symptoms in the cohort (%), whereas the bars on the left represent the time of onset after SARS-CoV-2 infection (mean ± SD). Articles:Mina, Y., Enose-Akahata, Y., Hammoud, D. A., Videckis, A. J., Narpala, S. R., O'Connell, S. E., Carroll, R., Lin, B. C., McMahan, C. C., Nair, G., Reoma, L. B., McDermott, A. B., Walitt, B., Jacobson, S., Goldstein, D. S., Smith, B. R., & Nath, A. (2023). Deep Phenotyping of Neurologic Postacute Sequelae of SARS-CoV-2 Infection. Neurology(R) Neuroimmunology & Neuroinflammation, 10(4), e200097. PubMed: Observational StudyNIH Press Release:  NIH study identifies features of Long COVID neurological symptoms                                                             Safety and clinical activity of autologous RNA chimeric antigen receptor T-cell therapy in myasthenia gravis (MG-001): a prospective, multicenter, open-label, non-randomized phase 1b/2a studyMyasthenia gravis (MG) is a chronic autoimmune disorder in which antibodies destroy the communication between nerves and muscle, resulting in weakness of the skeletal muscles. To address the limitations associated with the use of chimeric antigen receptor (CAR) T cells in individuals with autoimmune disease, Dr. Granit and colleagues engineered CAR-T cells, Descartes- 08, with RNA (rCAR-T) instead of the conventional DNA method, allowing for a short course of treatment that is given multiple times instead of the single-dose regimen normally used in DNA programmed CAR-T therapy. This novel approach was tested in individuals with MG: Descartes-08 appeared to be safe and well tolerated, showing clinically meaningful decreases in MG severity, indicating Descartes-08 as a useful, as-needed treatment. Though early data on the treatment’s effectiveness are promising, additional clinical studies are needed: Descartes-08 therapy is now being tested in a larger, clinical trial to determine its ability to reduce myasthenia gravis symptoms.Image: Colorized scanning electron micrograph of a T lymphocyte (also known as a T cell) (blue). Image source: NIAID Potential treatment for rare autoimmune disorder adapted from CAR-T therapy Articles:Granit, V., Benatar, M., Kurtoglu, M., Miljković, M. D., Chahin, N., Sahagian, G., Feinberg, M. H., Slansky, A., Vu, T., Jewell, C. M., Singer, M. S., Kalayoglu, M. V., Howard, J. F., Jr, Mozaffar, T., & MG-001 Study Team (2023). Safety and clinical activity of autologous RNA chimeric antigen receptor T-cell therapy in myasthenia gravis (MG-001): a prospective, multicentre, open-label, non-randomised phase 1b/2a study. The Lancet. Neurology, 22(7), 578–590. PubMed: Clinical TrialNIH Press Release:  Potential treatment for rare autoimmune disorder adapted from CAR-T therapy                                                             Identification of genetic risk loci and causal insights associated with Parkinson's disease in African and African admixed populations: a genome-wide association studyUsing a comprehensive Genome-Wide Association Study, Dr. Rizig and colleagues identified a novel genetic risk factor in GBA1 in people of African and African admixed ancestry, which has not been seen in European populations. The study revealed that that the GBA1 rs3115534-G variant, present in 39% of the sample, was linked to reduced glucocerebrosidase activity, a factor associated with the identified risk of Parkinson's disease. Moreover, the GBA1 rs3115534-G variant served as a modifier for age at onset of the disease. These results suggest that the GBA1 rs3115534-G variant could be a major mechanistic basis of Parkinson’s disease in African populations. The findings underscore the importance of inclusive representation of ancestrally diverse populations in genetic research.Image: Miami plot comparing European versus African and African admixed GWAS meta-analyses of Parkinson’s disease risk. Randomly sampled 1200 cases and 2445 controls were included in each of the GWAS meta-analyses. The grey horizontal lines indicate the significance threshold of 5 × 10–8. Articles:Rizig, M., Bandres-Ciga, S., Makarious, M. B., Ojo, O. O., Crea, P. W., Abiodun, O. V., Levine, K. S., Abubakar, S. A., Achoru, C. O., Vitale, D., Adeniji, O. A., Agabi, O. P., Koretsky, M. J., Agulanna, U., Hall, D. A., Akinyemi, R. O., Xie, T., Ali, M. W., Shamim, E. A., Ani-Osheku, I., ... Global Parkinson's Genetics Program (2023). Identification of genetic risk loci and causal insights associated with Parkinson's disease in African and African admixed populations: a genome-wide association study. The Lancet. Neurology, 22(11), 1015–1025.PubMed: Meta AnalysisNIH Press Release:  Parkinson’s disease gene variant found in study of some people of African ancestryExternal Press Release: Why is diversity in Parkinson’s research so important?New gene variant linked to Parkinson's disease found in people of African ancestryResearch Identifies Novel Genetic Risk Factor of Parkinson Disease in African Populations                                                             NINDS Health Equity Strategic Planning Process Overview, High-Level Recommendations, and GuideThe National Advisory Neurological Disorders and Stroke Council presented a comprehensive summary, outlining the direction for advancing the NINDS' health equity strategic planning initiative to eliminate disparities in neurologic conditions. Ten articles were identified to provide readers with context, evidence, and scientific reasoning for each of the 18 recommendations. The recommendations emphasize the need for increased research funding across all neurologic disease areas to identify and validate approaches to eliminate disparities. Strategies involve community engagement, training programs, and career development initiatives to promote diversity and inclusion in health equity research. The recommendations also emphasize the creation of tools, databases, and surveillance systems to enhance early detection, prevention, and evidence-based care for neurologic diseases in vulnerable populations. Image: Determinants of Inequities in Neurological Disease, Health, & Well-being: The NINDS Social Determinants of Health Framework for Addressing Health InequitiesImage Source: Griffith, D. M., Towfighi, A., Manson, S. M., Littlejohn, E. L., & Skolarus, L. E. (2023). Determinants of Inequities in Neurologic Disease, Health, and Well-being: The NINDS Social Determinants of Health Framework. Neurology, 101(7 Suppl 1), S75–S81.Articles:Johnston, K. C., & Trevathan, E. (2023). NINDS Health Equity Strategic Planning Process Overview, High-Level Recommendations, and Guide. Neurology, 101(7 Suppl 1), S1–S8.NIH Press Release: NINDS announces neurological health equity strategic planExternal Press Release: Neurological Health Equity: Research for All                                                             Monocyte-derived IL-6 programs microglia to rebuild damaged brain vasculatureCerebrovascular injury (CVI) can occur after infections, injury, stroke, neurodegeneration and autoimmune disease, resulting in damage to the surrounding brain tissues. In a study published in Nature Immunology, Dr. Bo-Ran Choi, a postdoctoral fellow in the lab of Dr. Dorian McGavern, found that CVI induces the generation of repair-associated microglia (RAMs) and that the number of RAMs is correlated with CVI severity. They demonstrated that infiltrating monocytes (a type of white blood cell) and interlukin-6 (a protein important for immune system signaling) are necessary for RAMs to be “programmed” to repair tissue after CVI. These data provide a molecular and cellular basis for how monocytes instruct microglia to repair brain vasculature and promote recovery after injury and suggest that future treatments aimed at increasing RAM numbers could help CVI patients.​Image: Figure 1B. Time lapse microscope images show microglia (Tmem119; green) interacting with blood vessels (Lectin; red) 30 minutes and 1 hour after CVI in vivo.​ White arrows indicate microglia extending processes toward a damaged vessel. Cyan arrows indicate microglia interactions with extravasated, lectin-derived material.Article: Choi, B. R., Johnson, K. R., Maric, D., & McGavern, D. B. (2023). Monocyte-derived IL-6 programs microglia to rebuild damaged brain vasculature. Nature immunology, 24(7), 1110–1123. PubMed                                                             Three papers shed light on mechanisms underlying TDP-43 proteinopathy​Abnormalities in the transcriptional repressor TAR DNA-binding protein-43 (TDP-43) are linked to amyotrophic lateral sclerosis (ALS), Alzheimer’s Disease (AD), frontotemporal dementia (FTD) and limbic-predominant age-related TDP-43 encephalopathy (LATE). This year, three seminal papers shed light on mechanisms of TDP-43 proteinopathy. Three seminal new papers investigate how TDP-43 dysfunction leads to misspliced “cryptic” RNAs. Estades Ayuso and colleagues show that the distribution of cryptic RNA accumulation in the brains of individuals with AD mimicked that of phosphorylated TDP-43, and that cryptic RNA accumulation could efficiently distinguish AD patients from controls. In a new preprint, Seddighi and colleagues show that TDP-43 depletion in iPSC-derived neurons leads to de novo “cryptic” peptides, altering protein-protein interactions. Many of these de novo peptides were also present in the cerebrospinal fluid of patients with ALS. Finally, Baughn and colleagues provide mechanistic insight into the function of TDP-43 and identify two methods to restore function of the protein stathmin-2 in motonuerons affected by TDP-43 pathology in vitro, laying the groundwork for the development of potential therapeutic approaches.​Images:TOP LEFT: Estades Ayuso et al. (2023) Figure 1A. TDP-43 staging scheme in Alzheimer’s disease.TOP RIGHT: Seddighi et al. (Preprint; 2023) Figure 2A.Illustration of  how RNA sequencing and proteomic methods were used for identifying “cryptic” exons and peptides in TDP-43 deficient neurons.BOTTOM: Baughn et al. (2023) Figure 4B. Microscope imaging showing in vitro axonal regeneration in neurons with TDP-43 pathology before rescue of the gene encoding stathmin-2. Left: Controls; Middle: TDP-43 pathology, Right: TDP pathology after treatment. Axons are labeled in red, stathmin-2 is labeled in green; yellow indicates areas of overlap.Estades Ayuso, V., Pickles, S., Todd, T., Yue, M., Jansen-West, K., Song, Y., González Bejarano, J., Rawlinson, B., DeTure, M., Graff-Radford, N. R., Boeve, B. F., Knopman, D. S., Petersen, R. C., Dickson, D. W., Josephs, K. A., Petrucelli, L., & Prudencio, M. (2023). TDP-43-regulated cryptic RNAs accumulate in Alzheimer's disease brains. Molecular neurodegeneration, 18(1), 57. PubMedSeddighi, S., Qi, Y. A., Brown, A. L., Wilkins, O. G., Bereda, C., Belair, C., Zhang, Y., Prudencio, M., Keuss, M. J., Khandeshi, A., Pickles, S., Hill, S. E., Hawrot, J., Ramos, D. M., Yuan, H., Roberts, J., Kelmer Sacramento, E., Shah, S. I., Nalls, M. A., Colon-Mercado, J., ... Ward, M. E. (2023). Mis-spliced transcripts generate de novo proteins in TDP-43-related ALS/FTD. bioRxiv : the preprint server for biology, 2023.01.23.525149.  PubMedBaughn, M. W., Melamed, Z., López-Erauskin, J., Beccari, M. S., Ling, K., Zuberi, A., Presa, M., Gonzalo-Gil, E., Maimon, R., Vazquez-Sanchez, S., Chaturvedi, S., Bravo-Hernández, M., Taupin, V., Moore, S., Artates, J. W., Acks, E., Ndayambaje, I. S., Agra de Almeida Quadros, A. R., Jafar-Nejad, P., Rigo, F., ... Cleveland, D. W. (2023). Mechanism of STMN2 cryptic splice-polyadenylation and its correction for TDP-43 proteinopathies. Science (New York, N.Y.), 379(6637), 1140–1149. PubMed                                                             A multi-laboratory preclinical trial in rodents to assess treatment candidates for acute ischemic stroke​Researchers have identified uric acid as a potential therapy to enhance recovery from acute ischemic stroke using a new method for conducting preclinical animal research. In the study, researchers from the National Institutes of Health’s Stroke Preclinical Assessment Network (SPAN) rigorously tested the effectiveness of six novel therapies in reducing ischemic brain injury in rodents using strategies normally reserved for clinical studies in humans.In addition to incorporating increased scientific rigor into preclinical testing, researchers used animal models that resembled typical stroke patients. The study included young mice and rats, aging mice, mice with diet-induced obesity or hyperglycemia, and rats with spontaneous hypertension, with equal numbers of males and females. (Visit A multi-laboratory preclinical trial in rodents to assess treatment candidates for acute ischemic stroke)​Image: Left: Figure 3A. Schematic showing the behavioral corner test used to assess whether rodents prefer to turn left or right when approaching a corner. Animals will preferentially turn to the side that is ipsilateral to the stroke location in their brain. Of the treatments tested, only uric acid (A) was above the efficacy boundary (top dotted line). Study arms: A, uric acid; B, tocilizumab; C, fingolimod; D, veliparib; E, fasudil.Lyden, P. D., Diniz, M. A., Bosetti, F., Lamb, J., Nagarkatti, K. A., Rogatko, A., Kim, S., Cabeen, R. P., Koenig, J. I., Akhter, K., Arbab, A. S., Avery, B. D., Beatty, H. E., Bibic, A., Cao, S., Simoes Braga Boisserand, L., Chamorro, A., Chauhan, A., Diaz-Perez, S., Dhandapani, K., ... Sansing, L. H. (2023). A multi-laboratory preclinical trial in rodents to assess treatment candidates for acute ischemic stroke. Science translational medicine, 15(714), eadg8656.Press release: Researchers develop new method to identify potential stroke therapies                         As we head into the new year at NINDS, it’s time again to reflect on all that has come and gone in the past twelve months. Even as we face complex challenges in neuroscience research and the diseases and conditions we hope to improve, I am proud of the progress we and our many partners have achieved. In 2023, NINDS supported and conducted research leading to new advances in basic, translational, and clinical neuroscience. While I cannot include all of them here, I have selected a few that you can view above, and I invite you to read about other highlights from the year below. We are grateful for the breadth of perspectives and expertise that made these and other accomplishments possible. BRAIN celebrates milestone achievements2023 marked 10 years since the White House first announced the Brain Research Through Advancing Innovative Neurotechnologies® Initiative, or The BRAIN Initiative®. The Initiative had as its singular focus to develop and apply “innovative technologies to construct a dynamic picture of brain function that integrates neuronal and circuit activity over time and space.” Over the past decade, the BRAIN Initiative has exceeded all expectations by energizing and accelerating interdisciplinary research to map, monitor and modulate brain circuits. The BRAIN Initiative’s initial strategic plan, articulated in the BRAIN 2025 report, set bold scientific goals that would propel neuroscience far into the future. In November, across 21 articles, the BRAIN Initiative Cell Atlas Network (BICAN) published comprehensive cell atlases of adult and developing human and non-human primate brains. The groundwork is now set to create a comprehensive connectome of the human brain. Just last month, the BRAIN Initiative Cell Census Network (BICCN) unveiled a complete cell atlas of the mouse brain, a momentous step forward toward one of BRAIN’s goals to completely characterize a mammalian brain. The resulting data and resources are now available to the research community to empower functional studies about brain function and brain disorders in both human and animal models of neuro/mental/substance abuse disorders.As highlighted in a recent message from NIH BRAIN Director Dr. John Ngai, the Initiative’s next transformative project, BRAIN Initiative Connectivity Across Scales (BRAIN CONNECTS) launched an initial set of awards to develop technologies to comprehensively map neural connections in both human and animal systems. Such “wiring diagrams” will be crucial for testing new hypotheses about how brain circuits function in health and disease. The BRAIN Initiative also continues to support innovative first-in-human trials using deep brain stimulation combined with artificial intelligence technologies that are showing great promise for the treatment of a variety of neurologic and neuropsychiatric disorders. In addition, the BRAIN Initiative is at the forefront of cross-cutting areas integral to advancing neuroscience research, including neuroinformatics, neuroethical considerations, and a commitment to enhance scientific excellence by increasing diversity and inclusivity in the research community. Our commitment to basic scienceNINDS support is unwavering for fundamental neuroscience (FN) research, which sets the foundation for discovery and progress against disorders of the nervous system. In 2023, the Fundamental Neuroscience Working Group (FNWG) of the National Advisory Neurological Disorders and Stroke (NANDS) Council, worked throughout much of the year to provide recommendations on how we can create opportunities to catalyze and accelerate discoveries in important fields of FN research. These efforts are essential as we seek new ways to stimulate innovation. As we now move to implement the WG’s recommendations, we do so in the context of the 2021-2026 NINDS Strategic Plan, which underscores the unique value of FN and our commitment to supporting investigator-initiated discovery research across the neuroscience spectrum. Strengthening our impact through community engagement2023 also saw the establishment of strategic priorities for amyotrophic lateral sclerosis (ALS) research(pdf, 1818 KB), through a NANDS Council Working Group comprised of scientists, clinicians, people living with ALS, people with genetic risk for ALS, and caregivers. We cannot underscore the urgency of this work enough, as ALS often occurs with no clear risk factors or family history, and the clock ticks quickly after symptom onset. As we address these strategic priorities, we also leverage important collaborations called for in the Accelerating Access to Critical Therapies, or ACT for ALS, including a Public-Private Partnership with the Food and Drug Administration (FDA) that includes multiple ALS non-profit organizations, the Critical Path for Rare Neurodegenerative Diseases (C-Path), the Foundation for NIH (fNIH), and multiple companies as partners in the effort to develop more effective treatments for persons with ALS. As part of this PPP, NINDS launched a national consortium of clinical research centers to carry out research within the PPP. I am especially grateful to those with lived experience of ALS that contributed to our strategic planning and the launch of the PPP, as their insights greatly enhanced and strengthened the Working Group’s recommendations.The value of bolstered community engagement has informed other NINDS activities, including the culmination of a NANDS Council Working Group on Health Disparities and Inequities in Neurological Disorders. This past summer, the group published findings and recommendations from a two-year strategic planning effort for health disparities and equity research in a special issue of Neurology. The work reflects a wide range of perspectives on the elimination of disparities and inequities in neurological care, outcomes, treatment, access and provision of services, and research. I encourage you to learn more about our next steps, including our new Community-Engaged Health Equity Research in Neuroscience Initiative. Leadership transitionsAs seasons come and go, they also bring bittersweet changes. This year, we celebrated the career and retirement of Dr. Kurt Fischbeck, whose research has focused on the underlying mechanisms of hereditary neurological and neuromuscular diseases. His colleague, Dr. Michael O’Donovan, also entered retirement, after a long career in the field of spinal motor circuits. In addition, after 24 years, Dr. Bob Finkelstein has retired as Director of the NINDS Division of Extramural Activities, where he oversaw extramural research for the Institute. These colleagues made tremendous contributions to neuroscience, NINDS, and NIH, and I wish them well in their new life chapters. Along with these transitions, we welcomed new faces and perspectives, including the appointment of Dr. Jeff Diamond as NINDS Scientific Director, who will provide overall executive direction and scientific leadership for the entire NINDS Intramural Research Program. He is joined by Dr. Faith Harrow Plante, who will direct the NINDS Office of Research, Training, and Career Development. Finally, I am excited for the leadership of new NIH Director Dr. Monica Bertagnolli, who transitions into the role after serving as Director of the National Cancer Institute. Moving into the new year, we look forward to a new NINDS Deputy Director – with endless thanks to Dr. Amy Bany Adams who has performed these duties in an acting capacity – and anticipate fresh vision and leadership to shepherd us into 2024.As we await Fiscal Year (FY) 2024 budget information, NINDS is currently operating under a Continuing Resolution through February 2, 2024, at the FY 2023 enacted funding level. We anticipate implementing a conservative funding strategy during this time. While this news can be challenging, I have witnessed the resilience of this community time and time again, and feel certain that our tenacity will guide us through these more uncertain times. Together, we will continue to move forward in service of our mission: pursuing important work to gain a deeper understanding of the brain and nervous system to develop effective therapies for all people.
- Neuroscience 2023 in Washington, D.C.:  Looking forward to connecting with our community! Neuroscience 2023 in Washington, D.C.:  Looking forward to connecting with our community!hsuns@nih.govMon, 11/06/2023 - 08:04            Monday, November 6, 2023                  As the leaves change colors this fall and 2023 rapidly comes to an end, Washington, D.C. will once again host the world's largest convening of neuroscientists at the annual meeting of the Society for Neuroscience, taking place from November 11-15. Simply put, it is one of my favorite times of the year as we benefit from front row seats to the latest cutting-edge scientific advances, take time to catch up with old friends, and connect with new NINDS grantees — especially the up-and-coming generation of neuroscience trainees. As our home base of Bethesda is a short distance away, NINDS will be out in full force at the meeting, and I'd like to share a few opportunities to meet our staff and get to know our Institute. Whether you can make it in person or not, please refer to our NINDS at Neuroscience 2023 event page that mirrors the content and opportunities shared at our onsite exhibit. This page will include information on our programs, initiatives, funding announcements, career opportunities, and other resources relevant to attendees of the annual Neuroscience meeting.For those attending in person, you can find NIH Institutes, Centers, and Offices supporting neuroscience research — including NINDS — at Booth #3401 in the main exhibit hall. Look for signs and scientific images of neurons and brains — you can't miss us! At the booth, you'll be able to: catch up on funding opportunities, learn about our programs and initiatives, meet one-on-one with NINDS program staff (via appointments which can be scheduled in advance), and even give us your honest feedback on how NINDS resources, including our website, could be more useful to you.Additionally, NINDS staff are hosting or involved in several scientific presentations and programs. Back by popular demand are several opportunities to learn how NINDS supports diversity in the neuroscience workforce, including:The 13th Annual Enhancing Neuroscience Diversity through: Undergraduate Research Education Experiences (ENDURE) Meeting (morning of Saturday, November 11);	The Diversity Poster Session featuring NINDS-supported trainees (evening of Saturday, November 11);	A session on “Building Up the Nerve” to Develop Your NIH Training Application (Monday, November 13); and	A reception celebrating our NINDS-supported diverse trainees and community (evening of Monday, November 13).recent strategic planning effort to advance health equity in neurological disorders, which I wrote about previously.You can also hear from our experts on research quality and rigor at a session on “Doing Our Part to Change the Culture of Science: Becoming a Champion for Rigor” (Saturday, November 11). That same day, you can also speak with NINDS staff and learn more about NIH’s new data management and sharing policy during the “Practical Guide to Data Management and Sharing Mandates” session. And, there will be many other opportunities to engage with NINDS staff and grantees in social settings, such as at the “Tools, Tech, & Theory: A BRAIN Initiative Alliance Social” and the U.S.-Japan Brain Research Cooperative Program (BRCP) Networking Session on Sunday, November 12, or during the “NINDS Therapeutic Development Projects: Posters and Discussions with Grantees and NIH Staff” (Tuesday, November 13). Timing and details on these sessions, and many more, are available on the NINDS at Neuroscience 2023 event page.Personally, I always look forward to hearing about the latest science, including from investigators supported through the NIH BRAIN Initiative. In the special lecture on Saturday, November 11 on “The Neuroscience of Dynamic Social Behavior: Uncovering Circuit Mechanisms in Drosophila,” Dr. Mala Murthy will discuss her work on developing a whole-brain connectome for the fly brain and understanding how the 130,000 neurons of the fly brain enable social interaction. I’m also excited to hear about the creation of new tools for neuroscience – a key goal of the NIH BRAIN Initiative – at the Albert and Ellen Grass Lecture on Monday, November 13 on the "Inner Workings of Channelrhodopsins and Nervous Systems" given by Dr. Karl Deisseroth. Dr. Deisseroth’s talk will provide insights on the fundamental survival drives of animals – such as thirst and hunger – at single-cell resolution, as well as the highest integrative functions of the brain.I am grateful for the steady and thoughtful return of in-person conferences and look forward to seeing many of you in Washington, D.C. soon. It’s a busy time for neuroscientists, but it’s one of the best ways to learn about all the new research going on in one place at one time. We are looking forward to connecting with you, so please say hello and introduce yourself to NINDS staff while you’re there!
- From Lab to Clinic: NINDS Support of Translational Research From Lab to Clinic: NINDS Support of Translational Researchhsuns@nih.govMon, 10/30/2023 - 13:11            Tuesday, October 31, 2023                  By Walter J. Koroshetz, M.D., Director, NINDS, Amir Tamiz, Ph.D., Director of the Division of Translational Research at NINDS, and Emily Caporello, Ph.D., Program Director, NINDS Small Business ProgramNINDS-funded science is the foundation that supports the development of new diagnostics and treatments for neurological disorders. However, advancing a therapeutic molecule or device from the laboratory to adoption by industry and then dissemination into healthcare is challenging and expensive. Along the way, researchers must overcome unique challenges to make sure novel products are safe and benefit patients. At NINDS, the Division of Translational Research (DTR)’s mission is to accelerate basic research findings towards patient use for neurological disorders and stroke by providing researchers in academia and biotechnology with funding, expertise, and resources using a diversity of programs. NINDS’s strategy is to fund investigators to obtain the data that would “de-risk” projects so that they can attract substantial private funding and move toward commercialization. We especially focus on developing treatments for conditions for which there is limited investment by the private sector, so that anyone with a neurologic disorder may benefit from NINDS-funded research.  Here, we highlight some of these programs, including the NINDS Small Business Program and translational research initiatives supported by the collaborative NIH Blueprint for Neuroscience.NINDS Small Business ProgramThe NINDS Small Business Program, part of the congressionally mandated National Institutes of Health (NIH) Small Business Program, encourages research and development that can lead to commercialization applications arising from neuroscience research. The program supports small businesses and start-ups whose innovative ideas run the gamut from applied bench research to early-stage human clinical trials. With over $83 million in funding available each year, the NINDS Small Business Program can support approximately 150 companies at any one time, many of which are early-stage spinouts formed from basic research discoveries at institutions, and who are working on turning discoveries into treatments. Small companies often need funding and resources to further develop initial discoveries into products that are ready for industry partnership and commercialization to ultimately reach patients who need them. Providing an early pillar of support for commercialization, the NINDS Small Business Program has two main components: the Small Business Innovation Research (SBIR) program and the Small Business Technology Transfer (STTR) program. Both use funding mechanisms to support projects and ideas across the spectrum of research and development from early-stage partnerships between universities and small businesses to business cooperative grants that have the option to fund limited-size clinical trials. Additionally, most of our programs offer non-dilutive funding and resources, which does not require business owners to give up equity as they further develop their ideas.For years, our small business program has helped bring several promising therapies closer to commercial application. Recently, we helped fund a clinical trial testing a variation of CAR-T cell therapy that aims to treat myasthenia gravis. We supported research for a variety of neurological conditions, injuries, and research tools that have led to success stories such as:Virtual reality therapies for stroke survivors;	Improved bike helmet designs that do a better job at preventing traumatic brain injury;	The development of more than 300 off-the-shelf research tools, including brain chemistry sensors, for studying the brain;	Supported development of a novel neuroprotective drug that is now approved for treatment of endometriosis and uterine fibrosis.In addition, NINDS leads oversight of the SBIR/STTR pain management programs through the Helping to End Addiction Long-term® Initiative (or NIH HEAL Initiative®). Here, the goal is to encourage the development of innovative and commercializable technologies and products that help diagnose and treat pain as well as improve pain management, by mitigating the limited amount of private investment in this space. Fourteen NIH Institutes, Centers and Offices currently participate in the HEAL SBIR/STTR pain management programs, which have provided approximately $60 million in funding to U.S. small businesses to date. Some recently funded projects include development of a novel therapy for migraine, a novel anesthesia guidance system, and a pain management technology for surgical patients.Translational Research Support through the NIH Blueprint for Neuroscience ResearchThe NINDS DTR also supports translational research programs for the NIH Blueprint for Neuroscience Research. This NIH-wide initiative with 12 collaborating Institutes, Centers, and Offices supports cross-cutting neuroscience activities aimed at accelerating transformative discoveries in brain function as it relates to health, aging, and disease, including a track for US small businesses. Two recently established programs of the NIH Blueprint are designed to further support important translational research.First, the NIH Blueprint Neurotherapeutics Network for Biologics (BPN-Biologics), built on the early success of BPN for Small Molecules, was developed with the recognition that there are considerable challenges involved in moving biologics discoveries (e.g., gene therapies, cell therapies, and antibodies) from a lab or small startup into a clinical setting. This process requires navigating complex issues regarding characterization, optimization, manufacturing (including good manufacturing principles), delivery, regulatory, and route of administration. The program has started six projects over the past year covering Muscular Dystrophies, Spinal Cord Injury, Glaucoma, and Epilepsy. BPN-Biologics supports successful biotherapeutic drug discovery and development as well as access to resources, including ones that facilitate connecting investigators with consultants with deep expertise in drug discovery and development to help funded investigators navigate through the preclinical development process. If you are interested in learning more about BPN-Biologics, you can view a recent webinar that provided a program overview and answered attendee questions.A second new translational research program of the NIH Blueprint is Blueprint MedTech, an NIH funded incubator program that aims to address challenges facing the development of groundbreaking medical device technologies. Blueprint MedTech was built to help catalyze the translation of discovery from early-stage development to clinical trial readiness, this time with a focus on medical devices. Blueprint MedTech, is structured into two main components:The Blueprint MedTech Incubator comprises two hubs—the Center for Innovative NeuroTech Advancement (CINTA) and NeuroTech Harbor (NTH)—that are funded by NIH to in turn provide funding and in-kind resources to innovator teams. The third cycle of funding through this program closed in August 2023, and the next solicitation is expected to be announced in February 2024.	The Blueprint MedTech Translator program includes two funding opportunities aimed at supporting investigators (through the UG3/UH3 mechanism) and small business concerns (SBCs; U44 mechanism) in their pursuit of translational activities and clinical feasibility studies that contribute to the development of therapeutic and diagnostic devices for disorders of the nervous system.  Blueprint MedTech supports many earlier-stage neurotechnology development efforts, in collaboration with CINTA and NTH to bring promising neurotechnologies to readiness for first-in-human clinical studies. NINDS recently funded three “Translator” projects through the Blueprint MedTech program:at-home hydrocephalus shunt monitoring, to reduce unnecessary emergency department visits, frequent invasive testing, and reduce inpatient stay duration;	a low-field magnetic resonance imaging (MRI) scanner for adaptive neurosurgical intraoperative imaging not possible with currently available technologies;	magnetic resonance (MR) image-guided focused ultrasound (MRgFUS) stimulation system – a noninvasive device-based neuromodulation system for non-addictive pain treatment.Together, these and other efforts at NINDS and across NIH bolster support for new technologies and treatments at a critical phase in the process of bringing them into clinical use. We encourage you to learn more about our translational research programs, including our small business program, as we work to accelerate fundamental basic research findings towards improving the health of those with neurological disorders and stroke.Related ResourcesBlueprint Neurotherapeutics Network (BPN) Biologics Resources
- Looking to the Future of Fundamental Neuroscience Looking to the Future of Fundamental Neurosciencehsuns@nih.govMon, 09/25/2023 - 11:54            Tuesday, September 26, 2023                  By Walter J. Koroshetz, M.D., Director, NINDS and Lyn Jakeman, Ph.D., Director of the Division of Neuroscience in Extramural Programs at NINDSThe nervous system is exceedingly complex and our lack of understanding of how it works stymies our efforts to develop treatments for neurological disorders. The brain, composed of 85 billion neurons and trillions of connections with an equal number of glial, vascular and immune cells, functions as an interrelated web to process information. Besides the connections within the nervous system, there is also a complex interplay with other body systems, especially since the nervous system supplies nerves to our organs. Nervous system cells themselves are unique in many ways: most dramatic are the long, sometimes feet long, thin processes that need to be nourished by cell bodies that are only a few microns in diameter. Understanding how the nervous system develops and carries out its complex functions is one of the greatest challenges in science and is critical for developing treatments for neurological disorders and diseases. While neuroscientists have made great discoveries since the days of Ramón y Cajal and colleagues, important fundamental questions remain. Since NINDS’s formation in 1950, we have long recognized the importance of supporting basic discovery or fundamental neuroscience (FN) research, and that work continues today. A great example is NINDS’s participation in the Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative that is revolutionizing our ability to understand how neural circuits process information. We are always seeking new ways to stimulate innovation and reinforce the bedrock of neurological advances through FN research. To address this goal, we recently convened a Fundamental Neuroscience Working Group (FNWG) of the National Advisory Neurological Disorders and Stroke (NANDS) Council to provide recommendations on how we can create opportunities to catalyze and accelerate discoveries in important fields of FN research. We are grateful to share that at our most recent Council meeting, the FNWG recommendations were approved.Recommendations from the Fundamental Neuroscience Working Group(pdf, 915 KB):	Prioritize research into the organization of macromolecular complexes within cells from a few nanometers to one micron in length by developing tools and research programs to create a dynamic Macromolecular Cartography that analyzes subsets of proteins known to be part of functional subcellular units.			Enable quantitative approaches to characterize protein and molecule turnover timescales and location in vivo to advance understanding of molecular interactions, their contribution to cellular stability and plasticity.			Support approaches for capturing and imaging cell movement and cell-cell interaction during development of the nervous system. 			Ensure adequate resourcing of tool development for in vivo measurement of cellular activity. 			Promote interdisciplinary team science and collaborations with technical expertise across diverse disciplines.			Support the mentoring of the next generation of FN researchers.	The FNWG was charged to: 1) look to the future of FN by identifying critical gaps, key unanswered questions, and new opportunities in FN research, 2) evaluate the effectiveness and potential of current NINDS programs to support the breadth of FN research, and 3) propose and prioritize concepts and strategies that could enhance the overall impact of NINDS FN research over the next 5-10 years.The FNWG, led by Drs. Yishi Jin and Timothy Ryan, included FN investigators from across the country. Given that FN research is characteristically driven by open curiosity and infinite topical areas, the group focused discussion on generating cross-cutting ideas and themes at the level of cellular and molecular neuroscience. This approach was motivated by the relatively untapped microscopic research scale, with a potential to be highly impactful in addressing a broad range of fundamental questions. To carry out their charge, the FNWG formed seven subgroups across cellular and molecular neuroscience domains, including: neural development; genomic organization and regulation; inter-tissue interactions; metabolism; lipid stasis; atomic organization of machinery; and subcellular organization of machinery. Each subgroup considered critical knowledge gaps, ideas to foster mechanistic investigation, technology hurdles, and perceived funding difficulties, towards an overarching goal of identifying high-priority themes and concepts that could be considered cross-cutting, with applications to many domains.The FNWG’s recommendations intend to advance a mechanistic understanding of neurobiology at the cellular and molecular level and to generate new hypotheses addressing the molecular machineries that form, drive, and maintain the organization and function of the nervous system. The first four recommendations focus on research tool development in cellular and molecular neuroscience with the FNWG’s consideration that technological solutions and microscopic capabilities are close to fruition for breakthroughs in these four areas. The FNWG conveyed that addressing common research bottlenecks can enable broad reaching opportunities for investigators seeking to pursue all sorts of research questions driven by individual curiosity. A similar approach has been taken to advance groundbreaking research spurred by the NIH BRAIN Initiative's focus on understanding neural circuits. The last two recommendations were considered absolutely essential for invigorating the current basic research workforce and community. FNWG recommended that NINDS support initiatives that enhance team science and cross-disciplinary efforts between neuroscientists and experts in other fields such as cell biology, protein chemistry and biophysics, as these cross-disciplinary approaches could be uniquely valuable to the proposed efforts. In the same vein, the FNWG recommended that NINDS support the cultivation and interdisciplinary training of a diverse pipeline of the next generation of FN scientists. This cultivation should begin specifically with support for and engagement of research at the undergraduate level and encompass trainees with diverse perspectives and broad interests. During Council discussion, some members wondered about the ability to facilitate research approaches that are spontaneous and untargeted as well as team science. Others were curious about whether a perceived emphasis on descriptive biology studies could also be reconciled with the focus on hypothesis testing to answer mechanistic questions. Alongside the recommendations, NINDS will explore these issues carefully as we work to implement the group’s recommendations, identifying how we can best foster fundamental neuroscience research for cellular and molecular neuroscience. In addition, we will be looking for opportunities and partnerships to support tool development and dissemination that can advance cellular and molecular neuroscience while continuing to support all areas of FN. We will work to identify ways to bring together diverse teams and trainees to address the big questions and challenges in FN.These recommendations complement the NINDS five-year strategic plan, which underscores the unique value of FN and our commitment to supporting investigator-initiated discovery research across the neuroscience spectrum. To help inform our implementation of the FNWG recommendations, we want to hear from you, too. In addition to the resources below, you are encouraged to submit comments to NINDS at fn@nih.gov regarding FNWG’s report or any points related to promoting FN research. We thank the Working Group members for their hard work over the last year, as well as the NINDS staff who facilitated and supported their deliberations. A richer understanding of all facets of fundamental neuroscience, including the cellular and molecular machineries that make up the nervous system, will benefit the entire neuroscience community and ultimately improve neurological health for all people.Related Resources:NANDSC Fundamental Neuroscience Working Group (FNWG)	Advancing Fundamental Neuroscience Research: Report of the Fundamental Neuroscience Working Group of the National Advisory Neurological Disorders and Stroke (NANDS) Council(pdf, 915 KB)	FNWG Draft Recommendations [presentation and discussion begins at 3 hours, 33 minutes]	FNWG Webinar – July 27, 2023
- September is Pain Awareness Month: We Are All in This Together September is Pain Awareness Month: We Are All in This Togetherhsuns@nih.govTue, 09/12/2023 - 07:39            Wednesday, September 13, 2023                  Each September, Pain Awareness month gives us an opportunity to reflect on the needs of the millions of people with chronic pain, as well as the research that we hope will better prevent and treat it. Chronic pain is highly persistent, with almost two-thirds (61.4%) of those who reported chronic pain in 2019 still reporting chronic pain a year later. There are more new cases of chronic pain in the United States per year than new cases of hypertension, depression or diabetes, according to research from the National Center for Complementary and Integrative Health (NCCIH). NIH supports a highly integrated, comprehensive research portfolio to address this pressing need. NINDS is one of many NIH Institutes, Centers, and Offices (ICOs) committed to understanding, preventing and treating pain. Because pain is a cross-cutting health problem, the ICOs work together to find solutions, including through the NIH Pain Consortium and the NIH Helping to End Addiction Long-term ® Initiative, or NIH HEAL Initiative®. Together, we strive to bridge the gaps between basic research, clinical trials, and implementation science towards meeting the needs of people living with chronic pain and co-occurring conditions. Importantly, NIH’s pain research efforts are guided by the wisdom and experience of those living with pain. A key priority of our current NINDS Strategic Plan(pdf, 1391 KB) is to increase patient engagement throughout the research process. None of this work would be possible without from the expertise of those who live with pain, including the HEAL Community Partner Committee (HCPC) and others who advise individual studies, as well as the people who volunteer to participate in studies and clinical trials. The NIH HEAL Initiative® recently launched a web page to promote patient and community engagement efforts and provide resources for researchers to help them involve “experience experts” as advisors and partners to their studies. During Pain Awareness month, NIH is partnering with the U.S. Pain Foundation on a webinar series connecting researchers with those living with pain. While pain is both a broad public health issue that we must work as a nation to address, it is also a series of individual circumstances that necessitate an individualized and whole-person approach to pain management. Each year, the NIH Pain Consortium hosts a symposium to highlight NIH-funded research related to pain. This year, we focused on Resilience and Pathways to Recovery, and on how whole-person health and a person’s environment affect pain. Members of the pain community shared their research showing how experiences with pain are unique and influenced by their social and physical environment, as well as the condition causing the pain, their genetic makeup, and their lived experience. Research underway Research from across the ICOs is improving our understanding of the biology underlying different pain conditions, identifying potential pain targets, and elucidating mechanisms that cause pain or deliver relief, and testing new treatment approaches:Researchers funded by NINDS and our partnering ICOs are uncovering potential new cellular targets that influence pain, identifying new molecules that could provide alternatives to opioids, and adapting known therapeutics in a way that might make them more effective against pain receptors. 	These new discoveries include identifying pathways in mouse models that can modulate pain-related behavior, and the brain circuitry that underlies how sound provides pain relief. Other research has found promising new targets that could ease chronic visceral pain. And researchers are finding promising new molecules that could lead to nonopioid pain therapies, and improving existing drugs in a way that could help better treat pain. 	Further along the research spectrum, clinical trials are building on advances made in preclinical research and are using novel technologies to reveal more about the pain experience and pain treatments. For example, a randomized clinical trial used imaging to show what parts of the brain played a role in providing the pain relief when engaging in mindfulness meditation. And in a small, early-stage study, a team of multidisciplinary researchers were able to identify signals in the brain that predicted chronic pain severity. Their findings suggest that a region of the brain called the orbitofrontal cortex might be an important mechanism in the perception of chronic pain.This last research finding is a great example of cross-NIH ICO collaboration at work – the tools for measuring brain activity were developed by the NIH BRAIN Initiative, and the study was additionally supported by NIH HEAL Initiative® funding to develop innovative devices for pain treatment. Neuroimaging research can supplement a person’s self-report of pain to find brain-specific causes of pain and to provide new research directions.This September, amid our search for safe and effective pain management approaches, we must also acknowledge the opioid crisis that continues to evolve in dangerous ways. Just a few weeks ago, we recognized the last day of August as Overdose Awareness Day, and September is also National Recovery Month. Overdoses and rates of substance use disorder have increased dramatically, further highlighting the need for alternatives to opioid analgesics. Research funded by our federal partners both at NIH and at other agencies show promising trends, but more must be done. The use of non-pharmacological treatments for those with chronic pain has been increasing, and more research is needed to maximize their efficacy. Broadening the availability of non-opioid treatments will empower people living with chronic pain to work with their providers in choosing the most effective and safest approaches to manage their pain.People make research possibleTo keep up the pace of discovery, we need to grow and support the pain research workforce and continue a commitment to the inclusion of unique perspectives in the research community. NINDS and the NIH HEAL Initiative® have developed several programs to help pain researchers gain more experience and connect with potential mentors and other scientists across the research spectrum. The PURPOSE Network (Positively Uniting Researchers of Pain to Opine, Synthesize & Engage) is a career development network that organizes an annual meeting and provides a collaborative online space for pain researchers to learn about new pain funding opportunities, career opportunities, peer networking, and ongoing education and training.To further foster education and training opportunities, the HEAL National K12 Clinical Pain Career Development Award provides protected research time for clinicians and scientists who come from institutions that may not be able to support the scholar’s research ambitions. Scholars will receive funding for their research and training, and they will be matched with mentors. The program will hold an information webinar on September 15, 2023, with full applications due February 5, 2024. The pain research community is more aligned than ever, but we still have a long way to go. NINDS and the other Institutes, Centers, and Offices across NIH are committed to listening to patients, communities, and scientists – towards ensuring that we support research that will improve our understanding of and deliver effective new treatments for pain.
- Making the untreatable treatable: the promise of gene-based therapies for neurological disorders Making the untreatable treatable: the promise of gene-based therapies for neurological disordershsuns@nih.govWed, 08/30/2023 - 09:27            Tuesday, September 5, 2023                  Earlier this summer, NINDS hosted our annual Nonprofit Forum, an annual event in which nonprofit leaders can network with colleagues and engage in discussions with NINDS staff. This year, considerable attention was paid to the emerging field of gene-targeted treatments for multiple neurological conditions. This cutting-edge area of science has opened a new window for the development of new therapies—particularly for disorders for which other drugs have had limited effects. These include well-established, rare, ultra-rare, or even yet undiagnosed neurological conditions for which NINDS is committed to developing treatments.Currently, about 30 cell and gene therapies are approved for use in the United States. NINDS- and NIH-funded research contributed to the development of Nusinersen (Spinraza®), which was approved in 2016 as the first treatment available for the inherited neurological disorder spinal muscular atrophy (SMA). This group of hereditary diseases can damage and kill motor neurons, which control movement in the arms, legs, face, chest, throat, and tongue, as well as skeletal muscle activity, such as speaking, walking, swallowing, and breathing. Beyond these therapies, many others are being studied and developed, and some like Skysona and Zolgensma have been recently approved by the U.S. Food and Drug Administration (FDA) to treat adrenoleukodystrophy and SMA, respectively. It is a promising time for gene therapy, but many families continue to see these devastating neurological diseases affect loved ones. More needs to be done to improve current therapies and bring new ones to patients.There is considerable enthusiasm for gene therapy to replace genes that don’t function or to use anti-sense oligonucleotides (ASO) to turn off mutated genes that cause damage. Indeed, recent technological advances have made it possible to accomplish both types of modifications. But no matter how exciting, we are still learning about how to best apply those techniques to make treatments both safe and effective. This is why NINDS is supporting multiple clinical trials through a variety of ongoing programs to advance genomic technologies and their applications.NINDS is also funding investigators to develop genomic therapies for rare and ultra-rare genetic diseases. The Ultra-rare Gene-based Therapy (URGenT) network was launched by NINDS in 2021 with the goal of supporting the development of state-of-the-art gene-based therapies for ultra-rare diseases—those that affect as few or fewer than one in fifty thousand people. An ongoing funding opportunity exists via the URGenT Network to help bring promising therapies into the clinic: the Translational Efforts to Advance Gene-based Therapies for Ultra-Rare Neurological and Neuromuscular Disorders U01. In addition, URGenT will be adding a gene therapy consortium to support clinical trials for ultra-rare diseases as part of a collaboration with the Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT).I am delighted to share that URGeNT has launched its inaugural set of awards. One team will leverage RNA technology to lower the amount of prion protein - a misfolding that results in a fatal and untreatable neurodegenerative disease. A second team will develop a lead candidate therapeutic - AAV9/AGA - as a treatment for Aspartylglucasaminuria, a devastating and currently untreatable neurodegenerative disorder. A third team will focus on developing a combination treatment for Menkes disease - an ultra-rare inherited disorder that presents early in life with progressive neurological decline. Collectively, these awards aim to accelerate therapeutic development with the goal of advancing safe and effective therapies.NINDS is also working with its public and private partners to advance genomic therapy for neurogenetic diseases, including through the Accelerating Medicines Partnership® (AMP®) program’s Bespoke Gene Therapy Consortium (BGTC). In May, the Foundation for the National Institutes of Health (FNIH), which manages the AMP BGTC program, announced the selection of eight rare diseases for inclusion in its gene therapy clinical trial portfolio. Among these are three neurologic disorders: Multiple Sulfatase Deficiency, Charcot-Marie-Tooth disease type 4J, as well as Spastic paraplegia 50 with Elpida Therapeutics. This is a massive effort comprising 33 member organizations, including 11 NIH Institutes and Centers, that has received more than $97 million in financial and in-kind commitments. The AMP goal is to develop a platform for gene therapy that will speed the process of addressing a number of rare disorders. This kind of support through the BGTC is necessary to address the needs of diseases too rare to fit within the traditional commercial therapeutic development pipeline.  In addition to knocking out harmful gene mutations or replacing missing genes, a new technology, called gene-editing, allows scientists to actually correct a mutation. This is done commonly in the laboratory in experimental models but is only in the clinical trial stage in altering a person’s blood cells to treat cancer or blood disorders. Begun in 2018, the Somatic Cell Genome Editing (SCGE) program is an initiative run through the NIH Common Fund aiming to create high-quality tools for safe and effective human genome editing. Earlier this year, Phase 2 of the program, which is co-chaired by NINDS and the National Center for Advancing Translational Sciences (NCATS) announced its first round of funded projects. The goal of Phase 2 is to accelerate the translation of genome editing therapies into the clinic, and will specifically focus on: developing technologies and assays for safety and efficacy studies; optimizing genome editing-based therapeutic leads to support advancement towards clinical trials; supporting novel genome editing clinical trials for more than one disease; and rostering collaboration and share new technologies and protocols with the public and research community. Another aspect of this phase of the SCGE program is the TARGETED Challenge, which aims to improve the state of gene editing technology, ultimately providing: 1) a programmable delivery system for gene editing, and 2) the means to cross the blood brain barrier, which is a significant hurdle to overcome when it comes to efficiently editing genes within the central nervous system. Registration for the challenge opened in May, and the Phase 1 deadline for applications is October 5, 2023. NINDS is also supporting those living with rare diseases through the Undiagnosed Diseases Network (UDN), a research program focused on gaining knowledge and finding answers to people and their families who have been unable to obtain a diagnosis. Beginning this year, NINDS will oversee the network in Phase III of the UDN, with help from 17 other NIH Institutes and Centers and the NIH Office of the Director. Although not directly linked to the development of gene editing therapies, the UDN could help us uncover new, rare diseases that could be targeted by such a therapeutic approach.Finally, labs right here at NINDS are also working to bring gene therapy into the clinic to treat previously untreatable disorders. The Neuromuscular and Neurogenetic Disorders of Childhood Section within the NINDS Division of Intramural Research aims to leverage genome editing to address early-onset neuromuscular disorders that develop during childhood. The group is currently recruiting participants for clinical trial readiness studies looking at two groups of early-onset dystrophies: COL6-related and LAMA2-related. Traditional drug-based approaches to therapies have served us well for a number of disorders, yet for many, promising treatments have remained elusive. With these NINDS- and NIH-supported clinical research efforts in the ever-evolving landscape of gene editing technologies, we have the opportunity to find new, more effective treatments for a variety of neurological conditions.
- Neurological Health Equity: Research for All Neurological Health Equity: Research for Allhsuns@nih.govSun, 08/13/2023 - 14:50            Tuesday, August 15, 2023                  Today, I am happy to announce that the findings and recommendations from our two-year strategic planning effort for health disparities and equity research are published in a special issue of Neurology. I extend my deepest thanks to the dozens of expert researchers and clinicians that served on a working group of the National Advisory Neurological Disorders and Stroke (NANDS) Council for Health Disparities and Inequities in Neurological Disorders. This working group of dedicated individuals went above and beyond, providing recommendations that were adopted by the NANDS Council, which the NANDS Council then provided to me. They have also produced a series of well-researched, in-depth articles addressing several interrelated topics, including social determinants of health (SDoH), community engaged research, diversifying the workforce, diversity, equity, inclusion, accessibility, and health equity research training, and public communication. The special issue serves as a guide for the neuroscience and neurological health community to identify and seize high impact opportunities to improve neurological health for all people, a core component of our mission statement. The priorities are an extension of the 2021-2026 NINDS Strategic Plan and are published with the expectation that future NINDS topical and disease-specific strategic plans will revisit these recommendations as applicable to different research areas. Most importantly, NINDS emphasizes the critical need to follow up data collection efforts with tests of interventions to enhance health equity. The recommendations focus on several interrelated topics:Social determinants of health (SDOH)	Community-engaged research approaches in clinical interventions	Neuroscience workforce diversity	Diversity, equity, inclusion, and accessibility (DEIA) and health inequities training	Communication and engagement with diverse communitiesFor the high level takeaways, visit the NINDS Strategic Plan and Recommendations for Advancing Health Equity in Neurological Disorders website and read the Executive Summary, which provides an excellent guide to the issue and lays out a set of consolidated, synthesized recommendations that cut across the sub-topics outlined above. The special issue also includes two additional studies; the results from an original analysis on lives lost due to disparities in neurological health and findings from a portfolio analysis and public stakeholder input, carried out by the working group and NINDS staff, respectively. Lastly, the working group presents a Social Determinants of Health Framework for Health Equity and its underlying principles. With this announcement, I’m pleased to formally adopt this model and encourage the entire NINDS research community to use it as a guide to design research that can improve the quality of neurological research and achieve neurologic health equity.               Image                              The NINDS Social Determinants of Health Framework for Addressing Health Inequities is a guide to improve the quality of neurological research, achieve neurologic health equity, and reach social justice. Download PDF version of the NINDS Social Determinants of Health (SDOH) Framework (pdf, 1363 KB)Now we turn to the important work of implementing the recommendations. Previously, we highlighted several health equity programs and workforce diversity efforts at our May 2023 Council Meeting. Dr. Richard Benson, Director of the Office of Global Health and Health Disparities, and Dr. Cheryse Sankar, Program Director in the Office of Global Health and Health Disparities, presented updates on NINDS’s health equity strategic plan implementation, which included efforts that stemmed from the working group’s recommendations on addressing social determinants of health, community engaged research, health equity research training, and capacity building. During the meeting, the Community-Engaged Health Equity Research in Neuroscience (HERN) initiative, NINDS’s largest health equity research program in several years, was approved. This new program is a multi-pronged initiative focused on understanding specific drivers of health disparities and barriers to equity; developing sustainable interventions; and enhancing training and capacity to conduct rigorous community-engaged research. Importantly, this initiative is agnostic to the neurological disease area of study. One working group recommendation is to involve community partners early and continuously throughout the research process. To ensure the success of HERN and related efforts, NINDS will provide new guidance on our expectations for conducting rigorous community engaged research, both for applicants and peer reviewers. As such, the Community Engaged Research Inclusion (CERI) plan will be required in HERN applications and other selected clinical research NOFOs, complementing the Plan to Enhance Diverse Perspectives, as initially piloted by the NIH BRAIN Initiative. The five year analysis of NINDS’s health equity research projects included in the Neurology issue made it crystal clear that we need to support more health equity projects across the board. Our goal now is to jumpstart the next generation of health equity neuroscience research. In addition to large scale initiatives like the HERN, several other initiatives and new projects have launched in the last 2 years. I’m especially excited to see that we’re beginning to receive applications with innovative approaches to address social determinants of health and structural racism. The working group advocated strongly for the need to improve the proportion of underrepresented minorities in the neuroscience and neurology workforce. As Dr. Michelle Jones-London, Director of NINDS’s Office of Programs to Enhance Neuroscience Workforce Diversity (OPEN), described during May Council, NINDS continues to add to and enhance our suite of programs to ensure a vibrant, talented, and diverse neuroscience workforce. These programs include Enhancing Neuroscience Diversity through Undergraduate Research Education Experiences (ENDURE), the NIH Blueprint and BRAIN Initiative Diversity Specialized Predoctoral to Postdoctoral Advancement in Neuroscience (D-SPAN) Award, and a new NOFO developed by NINDS with nine other Institutes and Centers, the Research Opportunities for New and "At-Risk" Investigators to Promote Workforce Diversity R01. These are just a few examples of what I believe are the most exciting collection of innovative workforce diversity efforts that NIH has to offer.Regarding public health communications, the working group stressed the importance of conducting formative research to better understand the target audience. To this end, I’m very proud of NINDS’s Mind Your Risks® campaign, which I highlighted earlier this year. Re-imagined in 2021, the campaign aims to raise awareness about the importance of controlling blood pressure among adult Black men ages 28 to 45, a population with an increased risk of high blood pressure, which can lead to stroke and dementia later in life.To begin exploring what we've come up with, I invite you to visit the strategic planning webpage and read the executive summary. Our efforts at NINDS are part of a wave of activity across NIH, including the groundbreaking work of the National Institute of Minority Health and Health Disparities, trans-institute efforts like NIH UNITE – an effort to end structural racism – and the Common Fund (see Transformative Research to Address Health Disparities and Advance Health Equity and Community Partnerships to Advance Science for Society (ComPASS)). As we work to carry out this important effort, I am reminded of a perspective article on health disparities in Stroke that Dr. Benson and I wrote, where we conveyed that  “The national conscience has opened to a new appreciation for the need for action to promote health equity and end the web of conditions that have perpetuated unhealthy disparities.” These collective efforts reflect our and NIH’s broader commitment to end structural racism and racial inequities throughout the biomedical research enterprise.Additional Resources and LinksSpecial Issue of Neurology	Media Advisory: NINDS announces neurological health equity strategic plan	January 2021 Director's Message	NANDS Council presentation in February 2022