As we look back on 2025, it is time to reflect on another year of progress, collaboration, and commitment across the neuroscience community. NINDS-supported researchers, clinicians, trainees, advocates, and partners advanced our understanding of the brain and nervous system and worked tirelessly to translate discovery into meaningful improvements for people living with disorders of the brain and nervous system. This year also marked a particularly meaningful moment in the Institute’s history—75 years of progress—offering both an opportunity to look back and a renewed focus on imagining our future. Our past and future owes deep gratitude to our tireless, compassionate, and dedicated former Director, Dr. Walter Koroshetz, whose leadership this past year in particular has been extraordinary and inspirational for every member of the NINDS family.
Top 10 NINDS Research Advances of 2025
Each year, NINDS highlights a selection of research advances that reflect the breadth, rigor, and impact of the science we support. The Top 10 NINDS Research Advances of 2025 span basic, translational, and clinical research and showcase progress across a wide range of neurological conditions and scientific approaches. Choosing a “top ten” list allows us to highlight a few remarkable advances, but they represent only a sliver of the amazing science we support. The annual advances by NINDS grantees help us understand what causes diseases and introduce innovative tools and treatments. Together, this information will improve prevention, diagnosis, and treatment for people affected by neurological disorders. They also underscore the creativity, perseverance, and collaboration that defines the neuroscience research community.
Continue Below to Read the Top 10 Research Advances
Celebrating 75 Years of Discovery and Progress
This year, NINDS marked a historic milestone with our 75th anniversary. Since our founding by Congress in 1950, NINDS has played a central role in expanding the frontiers of neuroscience, supporting discoveries that have transformed how we understand the nervous system and how neurological diseases are treated. As highlighted in the Director’s Message Celebrating 75 Years of Discovery and Progress these advances cross decades, from early insights into nerve signaling and brain development to more recent breakthroughs such as deep brain stimulation for movement disorders, clot-removal therapies for stroke, and groundbreaking gene-targeted approaches for rare neurological diseases.
Throughout the anniversary year, we celebrated this legacy through special events, historical features, and partnerships that brought the Institute’s story to life and honored the scientists, trainees, advocates, and research participants who made these achievements possible. Importantly, the 75th anniversary was not only a moment of reflection, but an opportunity to imagine a future in which we accelerate progress, embrace emerging technologies, and continue improving neurological health for people everywhere.
Progress Through Partnership: The NINDS Nonprofit Forum
Advancing neuroscience requires more than scientific excellence alone; It depends on strong partnerships and meaningful engagement with the people and communities we serve. In 2025, one of the year’s most impactful examples of collaboration was the NINDS Nonprofit Forum, highlighted in the Director’s Message Progress Through Partnership: Highlights from the 2025 NINDS Nonprofit Forum. The Forum brought together patient advocates, nonprofit leaders, researchers, and federal partners for a day of dialogue, shared learning, and strategic discussion.
Conversations throughout the Forum emphasized the critical role of nonprofit organizations and patient communities in our ability to shape research priorities, accelerate translation, and make sure that scientific advances stay focused on real-people’s needs. Truly open exchange amplifies our impact and helps us align scientific progress with the experiences and priorities of people living with neurological conditions.
Funding and Strategy
Sustaining scientific progress and positioning the field for future advances requires thoughtful, strategic investment in neuroscience research. Throughout 2025, NINDS continued to support a broad and impactful research portfolio while navigating a dynamic funding environment. In the Director’s Message NINDS’s Approach to Funding Neuroscience Research in 2026, we outlined how the Institute is adapting to evolving NIH policies and fiscal realities while remaining committed to scientific excellence, fairness, and transparency.
Our funding approach prioritizes a strong foundation of investigator-initiated research, relies on high quality peer review, supports translation from discovery to clinical impact, and invests in workforce development, with particular attention to protecting early-stage investigators. Even as funding processes and conditions continue to evolve, NINDS remains focused on balancing stability with innovation, using available resources thoughtfully to maximize scientific opportunity and public health benefit.
Looking Ahead with Gratitude
None of the progress highlighted here would be possible without the dedication and collaboration of our grantees, trainees, research participants, partners, advocates, and staff. Your creativity, perseverance, compassion, and commitment to moving neuroscience forward continue to drive discovery and translate knowledge into meaningful improvements in neurological health. We are deeply grateful for the passion and care you bring to this work every day. Thank you for your continued partnership and for all that you do to advance the mission of NINDS.
As we reflect on the close of this year, we also want to share that we are deeply proud of the resilience, independence, and focus the neuroscience community has shown—especially in times of challenge—and of the progress you continue to drive on behalf of people living with neurological disorders.
Progress To Slow Disability in Non-Relapsing Progressive Multiple Sclerosis
Many drugs prevent relapses, or flare-ups, in people with multiple sclerosis (MS). Non-relapsing secondary progressive MS is a form of the disease where symptoms grow worse over time without remitting/relapsing, and no approved treatments are available. A phase 3 clinical trial conducted in collaboration with the NINDS intramural program has shown that participants who took Tolebrutinib (Bruton’s tyrosine kinase (BTK) inhibitor), a new type of drug that reaches the brain, slowed disability progression compared to participants who took a placebo. The results suggest a new treatment target: B cells, which can produce antibodies within the central nervous system that may help people in later stages of MS as well as slow progression of disability in progressive MS.
Tolebrutinib in Nonrelapsing Secondary Progressive Multiple Sclerosis
How Neurons Precisely Control the Timing of Electrical Signals
Neurons rely on precisely timed electrical signals to communicate. This timing depends on the rapid opening and inactivation of ion channels. This study explains the structural mechanisms underlying fast N-type inactivation in voltage-gated potassium channels, a key process that controls neuronal firing and synaptic signaling. By determining how channel structure enables rapid inactivation, this work advances our fundamental understanding of neuronal communication and provides a framework for interpreting how disruptions in these channels may contribute to neurological disease.
Structural basis of fast N-type inactivation in Kv channels
Clarifying TDP-43’s Role in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD)
Abnormalities in the cell protein TDP-43 are a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This study demonstrates that loss of TDP-43 from the cell nucleus is associated with widespread changes in RNA alternative polyadenylation (APA), a physical modification to the RNA that impacts how genes are turned on and off in the cell. These findings broaden understanding of how TDP-43 dysfunction alters gene control in neurodegenerative disease and implicate RNA metabolism as a key contributor to disease mechanisms.
TDP-43 nuclear loss in FTD/ALS causes widespread alternative polyadenylation changes
How Brain Lipids May Influence Neurodegeneration (combined advance)
Brain lipids are fatty molecules that build and protect brain cells: 60% of the brain is composed of lipids. Together, two recent studies show how brain lipid metabolism is an important factor in neurodegeneration. One study shows that certain types of brain lipids (neuronal polyunsaturated fatty acids) help brain cells resist damage in models of ALS and FTD. The second study identifies a protein found in protective glial cells (called Obp44a) that helps control how brain lipids are made and maintained. Viewed together, these findings highlight how both neurons and glia work together to control brain lipid health and suggest new avenues for understanding and potentially modifying neurodegenerative disease risk.
Neuronal polyunsaturated fatty acids are protective in ALS/FTD
Glia-derived noncanonical fatty acid binding protein modulates brain lipid storage and clearance
Changes in DNA Over Time, Not Just Inherited Mutations, Drive Huntington’s Disease (HD) (combined advance)
These three complementary studies strengthen evidence that gradual growth of the CAG repeat that people with HD inherited from their parents plays a central role in HD onset and progression. The healthy Huningtin gene (Htt) carries CAG repeats. These are like repeated words in a in a gene sentence, and they serve a normal function in the Htt gene. An Htt gene with an abnormally expanded CAG repeat causes the disease. Expanded CAG repeats (Htt gene sentences with too many repeated CAGs) can be inherited, but the CAG repeats are instable, and can continue to expand throughout life (called “somatic repeat expansion”). One study, which used tissue from the NIH NeuroBioBank, links the somatic expansions of the inherited CAG repeat in the brains of people with HD to neurodegeneration, while two additional studies focus on genes, including those that repair broken DNA, that help control how quickly CAG repeats grow over a person’s lifespan. Together, these important studies reframe HD as a disorder driven in part by dynamic genetic instability and point to completely novel potential therapeutic strategies in HD focused on blocking somatic repeat expansion.
Long somatic DNA-repeat expansion drives neurodegeneration in Huntington's disease
Distinct mismatch-repair complex genes set neuronal CAG-repeat expansion rate to drive selective pathogenesis in HD mice
In vivo CRISPR-Cas9 genome editing in mice identifies genetic modifiers of somatic CAG repeat instability in Huntington's disease
New Research Shows Benefit of Surgery for Idiopathic Normal-Pressure Hydrocephalus
Idiopathic normal-pressure hydrocephalus (iNPH) is an often-misdiagnosed condition that causes problems with walking, thinking, and bladder control. Until now, few treatment options have been verified by clinical research. This randomized clinical trial tests the effects of shunt surgery in people with iNPH. In this procedure, a surgeon implants a small tube into the brain to drain extra fluid that is causing symptoms. The study provides important evidence to guide diagnosis and treatment decisions for managing a condition that is often underrecognized.
A Randomized Trial of Shunting for Idiopathic Normal-Pressure Hydrocephalus
New Evidence Helps Physicians Choose the Safest Way to Prevent Stroke Before Symptoms Appear
As we learn more about how to prevent strokes, one key question is how to reduce stroke risk in people who have severe narrowing in their neck arteries but are not having any stroke symptoms. This study compared two groups of patients: one group who received standard medical therapy to another group who received the same treatment but also had a small tube - called a stent - inserted into their neck artery to open it up. Overall, the results show that introducing a stent had the most effect on limiting stroke risk. This information is critical for helping determine which treatment approach is most safe and effective in preventing a future stroke. The results will have a significant impact on how physicians make recommendations for individual patients.
Medical Management and Revascularization for Asymptomatic Carotid Stenosis
Adaptive Brain Stimulation Helps Preserve Brain Function in Epilepsy
Some people with epilepsy that do not respond to medical treatment have a special device implanted into their brain, which can be used to stop abnormal brain activity common during seizures. This study (in a rat model) tested use of a device programmed to automatically correct abnormal electrical activity in rats who have epilepsy. The study showed that rats with the self-correcting device had fewer epilepsy-caused brain problems. By targeting epilepsy-related brain electrical signaling rather than seizures alone, this work is an important step toward developing neuromodulation strategies in people that preserve brain function and preventing disease progression.
Closed-loop electrical stimulation prevents focal epilepsy progression and long-term memory impairment
What We Eat Can Shape the Brain’s Internal Clock
Circadian rhythms—the body’s internal clock— are affected by many things including not only time of day but also other factors like what we eat. This study, in mice, shows that certain types of dietary fats (unsaturated fats) had effects on a key protein important for function of the body clock. By changing lighting schedules in the mice’s surroundings, the researchers simulated different seasons of the year. The study shows that diet (the unsaturated fats) affected how well the mice adapted to seasonal changes. The findings improve understanding around how metabolism and circadian rhythms interact, with implications for brain health in people where dietary and light cues don’t always match up such as shift work or jet lag.
Unsaturated fat alters clock phosphorylation to align rhythms to the season in mice
Detailed Map of the Developing Human Brain Opens New Doors for Understanding Brain Disorders
A groundbreaking collection of new studies provides the most comprehensive picture to date of how the human brain develops from its earliest days. The new information provides critical insights for understanding neurodevelopmental disorders such as autism, ADHD, and hundreds of other conditions that affect learning, language, and movement. This progress comes from many different scientists working across the country who are funded by the NIH’s Brain Research Through Advancing Innovative Neurotechnologies® Initiative, or The BRAIN Initiative®. The studies used state-of-the-art single-cell and spatial genomic approaches and also identified genetic switches that turn genes on or off in specific cell types as the brain is forming. The research, which is available to scientists everywhere, establishes critical infrastructure and data sets to foster future discovery across neuroscience.
BICAN: A cell census of the developing human brain.
Image Credit: Rozell C et al. Decoding Depression. BRAIN Initiative Photo & Video Contest. 2024.
