Goal #1: Advance clinical and translational science

<h4>Mayo Clinic scientists are pushing medicine beyond diagnosis, developing treatments for ultrarare genetic diseases while building a model that could accelerate the path to treatment for many more.&nbsp;</h4>Behind the glass walls of her <a target="_blank" rel="noreferrer noopener" href="https://www.mayoclinic.org/">Mayo Clinic</a> neuroscience laboratory, <a target="_blank" rel="noreferrer noopener" href="https://www.mayo.edu/research/faculty/cousin-margot-a-ph-d/bio-20503541">Margot Cousin, Ph.D.</a>, watches tiny clusters of living neurons flicker across her computer screen. Magnified hundreds of times, the cells carry the genetic variant responsible for <a target="_blank" rel="noreferrer noopener" href="https://rarediseases.org/rare-diseases/kcnk9-imprinting-syndrome/">KCNK9 imprinting syndrome</a>, one of the rarest neurological diseases in the world.Dr. Cousin directs Mayo Clinic's N-of-1 Therapeutics Program, where scientists develop treatment strategies for diseases so rare they may affect only a single person. Each advance can help shorten the path for the next ultrarare disease, and the one after that."For decades, the greatest success we could offer many patients was finally putting a name to their disease," says Dr. Cousin, a clinical and translational scientist in <a target="_blank" rel="noreferrer noopener" href="https://www.mayo.edu/research/centers-programs/center-individualized-medicine">Mayo Clinic's Center for Individualized Medicine</a>. "A diagnosis is an extraordinary achievement, but it's no longer the end of the journey. The future of medicine is turning that diagnosis into a path toward treatment." Read full article…

Mayo Clinic Center for Clinical and Translational Science

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Mayo Clinic Rochester

Margot Cousin, Ph.D., a clinical and translational scientist in Mayo Clinic’s Center for Individualized Medicine, directs the N-of-1 Therapeutics Program, which develops treatment strategies for ultrarare genetic diseases. Her laboratory combines genetics, disease modeling, molecular therapeutics and artificial intelligence to move patients from diagnosis toward treatment. A major focus is KCNK9 imprinting syndrome, a neurological disorder affecting fewer than 100 known people worldwide. In 2022, her team identified 15 previously unknown disease-causing genetic changes, providing diagnoses for 21 families. The team is studying disease progression and potential therapies, including antisense oligonucleotides. Dr. Cousin and collaborators also helped deliver the first custom experimental genetic treatments for a Mayo Clinic patient with Autosomal Dominant Leukodystrophy in 2025. The article does not provide her educational background or prior training.

One Patient at a Time, Mayo Clinic KL2 Scholar Takes on World’s Rarest Diseases 

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Goal #3: Address health needs of populations

A simple change in when people eat may offer a promising new approach for Huntington’s disease, according to research led by Oregon Health &amp; Science University.In a 12-week pilot study, researchers found that people with early-stage <a target="_blank" rel="noopener noreferrer" class="externallink" href="https://www.ohsu.edu/brain-institute/other-movement-disorders">Huntington’s disease</a> were able to safely follow a form of intermittent fasting known as time-restricted eating, limiting food consumption to a six-to-eight-hour window each day. Participants avoided unintended weight loss and showed improvements in measures of disease severity; in a blood biomarker linked to nerve cell damage; and in cellular energy production.The findings, <a target="_blank" rel="" class="externallink" href="https://www.nature.com/articles/s42255-026-01612-x" title="">published today</a> in Nature Metabolism, represent the first clinical study to test time-restricted eating in people with Huntington’s disease.“This is the first time this approach has been formally studied in people with Huntington’s disease,” said Russell Wells, a fourth-year OHSU medical student and lead author of the study. “We found that participants were able to follow the eating schedule, maintain their weight and show encouraging improvements in clinical and biological measures that are important in Huntington’s disease. These results suggest time-restricted eating deserves further study in a larger clinical trial.”Huntington’s disease is a rare, inherited neurological disease that gradually damages nerve cells responsible for movement, cognitive and emotional regulation. Wells said it can be compared to having Parkinson’s disease, Alzheimer’s disease and ALS at the same time.The condition affects about 41,000 Americans, while more than 200,000 others are at risk because they have a family history of the disease, according to the Huntington’s Disease Society of America. Each child of a parent with Huntington's disease has a 50% chance of inheriting the gene mutation that causes the disorder. Symptoms typically begin between ages 30 and 50 and worsen over 10 to 25 years.Although researchers have known the genetic cause of the disease for decades, no treatments have been approved that slow or stop its progression.<h2>Intermittent fasting</h2>The idea for the study grew out of earlier research in animal models showing that intermittent fasting can activate cellular pathways that help protect brain cells. Yet researchers were unsure whether the approach would be safe for people with Huntington’s disease because unintended weight loss is already a concern.Those concerns initially gave senior author Amie Hiller, M.D., pause. Hiller is professor of neurology in the OHSU School of Medicine and director of the Portland Veterans Administration Northwest Parkinson's Disease Research, Education and Clinical Center.“When Russell first brought me the idea, I was skeptical,” Hiller said. “Weight loss is a major challenge for many people with Huntington’s disease, so asking them to eat within a limited time window seemed counterintuitive.“What was exciting about this study is that participants were able to maintain their weight while showing signs that the intervention may be positively affecting the disease itself.”The study enrolled 20 adults with early-stage Huntington’s disease. Participants selected an eating window that fit their daily routine, typically between late morning and early evening, and followed it for 12 weeks. Researchers encouraged participants to maintain their normal calorie intake and monitored weight and safety throughout the study.The approach appeared well-tolerated. Participants followed the eating schedule on average more than five days per week; reported few side effects; and maintained both body weight and lean muscle mass. Most adapted to the schedule within the first one to two weeks.Amie Hiller, M.D., left, patient Anna White, and Russell Wells, a fourth-year OHSU medical student, in an exam room at OHSU in Portland, Oregon.&nbsp;Hiller and Wells are researching whether intermittent fasting could improve symptoms associated with Huntington's disease. (OHSU/Christine Torres Hicks)For study participant Anna White of Portland, adapting to the eating schedule turned out to be easier than expected.“When Russell called me a few years ago and asked if I would be interested in this trial, I jumped at the chance,” White said. “I had been interested in intermittent fasting for a while because it is a much friendlier way to initiate autophagy by restricting the time of eating, rather than what you eat.”White, who had previously followed a ketogenic diet in hopes of slowing Huntington's disease progression, said she initially wondered whether the fasting schedule would be difficult to maintain.“I was worried that I would struggle with the fasting part, but it became pretty easy and sort of matches my own hunger window,” she said. “I am never hungry for breakfast anyway, so I could start my eating at 11 a.m. and finish by 5 to 7 p.m. easily.”Participants used a smartphone app to document their first meal of the day with a photo and timestamp. White said she appreciated being able to eat foods she enjoyed while monitoring her weight throughout the study.“I could eat whatever I liked and, because I was weighing myself several times a week, I felt confident that my weight was staying very stable,” she said.<h2>Signs of progress</h2>Researchers found encouraging signals that the dietary intervention could influence disease progression.Participants experienced an average improvement of 0.5 points on a widely used Huntington’s disease severity scale known as the composite Unified Huntington’s Disease Rating Scale, or cUHDRS. The score typically declines by about one point annually in people with early-stage disease.In addition, blood levels of neurofilament light, a biomarker released when nerve cells are damaged, fell by an average of 13%. In Huntington’s disease, those levels usually increase over time as the disease progresses.“We saw a reversal of the trend we would normally expect,” Wells said. “Neurofilament light typically rises as neurodegeneration continues, but after three months we observed a significant decrease. For a pilot study, that was a remarkable finding.”White has continued practicing time-restricted eating since the study ended and believes it has helped her maintain cognitive function.“Many people have told me that for a 52-year-old woman with as much movement as I have, I am still self-aware and sharp,” White said. “I try to finish The New York Times crossword puzzle every day, and I think the time-restricted eating has helped.”The research team also examined mitochondrial function in participants’ blood cells. Mitochondria generate energy for cells, and impaired energy production is a hallmark of Huntington’s disease.Researchers found improvements in several measures of mitochondrial activity after the intervention.“One theory is that fasting acts as a mild stressor that prompts cells to become more efficient,” Wells said. “If cells, including brain cells, become better at producing energy and handling stress, they may be more resilient to the disease process.”Because the study was small and did not include a comparison group, researchers caution that the findings should not be considered proof that time-restricted eating slows Huntington’s disease. Larger, randomized controlled trials will be needed to determine whether the benefits are real and sustained over time.Still, researchers say the results are especially promising because the intervention is relatively simple and could be accessible to many people.“We do not currently have any disease-modifying treatments for Huntington’s disease,” Hiller said. “If future studies confirm these findings, this could become an approach available to people regardless of where they live or their financial resources. That makes it particularly exciting.”The team is currently pursuing funding for a larger, randomized clinical trial that would compare time-restricted eating with standard dietary habits.For Wells, the study represents an important step toward finding practical strategies that could help people before symptoms become severe and debilitating.“One of the unique aspects of Huntington’s disease is that some people know years in advance that they carry the genetic mutation,” Wells said. “That creates a window of opportunity to explore interventions that might delay onset or slow progression. Lifestyle approaches such as time-restricted eating could someday become an important part of that strategy.”In addition to Wells and Hiller, OHSU co-authors on the study include Andrew McHill, Ph.D., Nora Gray, Ph.D., and Joseph Quinn, M.D., as well as Lee Neilson, M.D., with the University of Iowa and VA Iowa City Healthcare System.The researchers acknowledge the help of the OHSU Oregon Clinical and Translational Research Institute for input on the trial design and OHSU Biostatistics and Design Program for data analysis expertise.This research was supported by an OHSU Parkinson Center of Oregon pilot award, Department of Veterans Affairs Clinical Science Research and Development Career Development Award-2 (CDA-2) grant CX00253, the Parkinson’s Disease Research, Education, Clinical Center at the VA Portland Health Care System, and by the National Center for Advancing Translational Sciences, National Institutes of Health, through award numbers TL1TR002371 and UL1TR002369. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other funders.

Oregon Clinical and Translational Research Institute

Russell documents a patient's progress as she points to different colors on a sheet of paper and says what they are at an OHSU exam room.

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Oregon Health & Science University

An OHSU-led pilot study suggests that time-restricted eating, a form of intermittent fasting, may offer a promising new approach for slowing progression of Huntington’s disease. Published in Nature Metabolism, the 12-week study enrolled 20 adults with early-stage Huntington’s disease and found that participants were able to safely limit eating to a six-to-eight-hour daily window while maintaining weight and lean muscle mass. Researchers observed improvements in disease severity measures, a 13% reduction in neurofilament light, a blood biomarker associated with nerve cell damage, and enhanced cellular energy production. The study was led by Russell Wells, with support from OHSU’s Oregon Clinical and Translational Research Institute (OCTRI), the institution’s CTSA hub. While larger randomized trials are needed, the findings highlight the potential of a low-cost, accessible lifestyle intervention to improve outcomes for people living with this progressive neurodegenerative disease.

Intermittent Fasting Shows Promise in Slowing Huntington’s Disease Progression, in Study Led by TL1 Trainee

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Goal #7:  Training and career support programs for translational scientists

Naomi Carter has a mission, and she'll tell you exactly what it is."My mission is to improve how we treat patients. That is why I wake up every day. It's why I work hard. It's why I mentor. It's why I teach."Carter is a fourth-year M.D.-Ph.D. student in the <a target="_blank" rel="noopener noreferrer" href="https://medschool.vcu.edu/education/graduate/dual-degree/mdphd/">Medical Scientist Training Program</a> at Virginia Commonwealth University's School of Medicine and a scholar in the<a target="_blank" rel="noopener noreferrer" href="https://cctr.vcu.edu/education-and-training/t32-training-program/"> Wright Center's Translational Biomedical Sciences T32 Training Program</a>, a fellowship designed to deepen training in translational science and community-engaged research alongside doctoral work."Translational science is when you're trying to go from the bench — research in a lab — to research in humans that is helpful to people," she said. "And there are a lot of little barriers that exist between these two mediums."Her own research targets one of those barriers directly."About 25% of Americans have chronic pain," she said. "That is a huge number." Despite decades of research and billions of dollars in federal funding, less than 1% of clinical trials testing drugs to treat chronic pain succeed. Carter wants to know why."My research is looking at the bumps and barriers and walls between our preclinical research and our clinical research in humans and asking the question, how can we knock those down?" she said. "So that next time when something works preclinically, it actually does work in people."Her work is particularly focused on interstitial cystitis, also known as chronic bladder pain syndrome — a condition affecting roughly 10% of women for which no new therapy has been approved since 1996. "That is before I was born," Carter noted. "So we have a lot of work to do."<h2 style="text-align: left;">From the ambulance to the lab</h2>Carter's path to research started in the back of an ambulance.Growing up in Maryland with a pediatrician mother, she was drawn to medicine early. But becoming an EMT in high school first put her face-to-face with what would become her life's work."When patients call 9-1-1, when they call an ambulance, they are likely having their worst day. The ability to work with them and help take care of those patients was an honor and something that I found really fulfilling." But after dropping patients off, she said, "that was the end of patient care, and I found that frustrating. I wanted to provide extended treatment and continue working with patients."That frustration led her to Hampton University, a historically Black university she describes as "a phenomenal experience," where her freshman biology professor convinced her to explore the MARC program, an NIH-funded initiative aimed at getting students from minority backgrounds into Ph.D. and M.D.-Ph.D. programs."After many, many no’s, she convinced me to go to one of the program meetings. I got intrigued with research, and I started to get a feel for how that could impact my career and impact the people I want to treat." Starting to do research, even in her freshman year, she was hooked.“I just fell in love with it,” she said."I remember walking on campus and thinking, I really like research and I really like medicine. And I think the best thing for me to do is to do both."<h2 style="text-align: left;">Working with mentors</h2>At VCU, Carter works with two mentors: <a target="_blank" rel="noopener noreferrer" href="https://pharmtox.vcu.edu/about/directory/s-stevens-negus-phd.html">S. Stevens Negus, Ph.D.</a>, a professor in the <a target="_blank" rel="noopener noreferrer" href="https://pharmtox.vcu.edu/">Department of Pharmacology and Toxicology</a> in the <a target="_blank" rel="noopener noreferrer" href="https://medschool.vcu.edu/">VCU School of Medicine</a> whose lab specializes in behavioral pharmacology and opioid research; and <a target="_blank" rel="noopener noreferrer" href="https://obgyn.vcu.edu/about/our-team/julie-suyama-md-phd.html">Julie Suyama, M.D., Ph.D.,</a> a urogynecologist in the <a target="_blank" rel="noopener noreferrer" href="https://obgyn.vcu.edu/about/our-team/">Department of Obstetrics and Gynecology</a> in the <a target="_blank" rel="noopener noreferrer" href="https://medschool.vcu.edu/">VCU School of Medicine</a>, with deep expertise in interstitial cystitis."Together I have an excellent team of people who can support me in my work, which is to conduct preclinical research and clinical research on pain assessments in preclinical models of and patients with interstitial cystitis," Carter said. "Dr. Negus provides expertise on how we can assess pain preclinically, and Dr. Suyama provides the expertise on how to assess pain in patients."<h2 style="text-align: left;">Securing independent research funding</h2>The T32 is designed to do more than pay a stipend. It requires trainees to develop and submit an extramural grant for their dissertation research and provides students with internal feedback on their grant before it goes to the NIH. "They'll review that grant and provide you with feedback before you submit it," Carter said.This summer, Carter was awarded an NIH Ruth L. Kirschstein F30 predoctoral fellowship from the National Institute of Diabetes and Digestive and Kidney Diseases. The F30 fellowship, a highly competitive fellowship meant to support independent training for M.D.-Ph.D. students, will support both the preclinical and clinical arms of her work on pain assessment, exactly the transition from institutional training grant to independent funding that the T32 is built to produce.<h2 style="text-align: left;">A physician-scientist's calling</h2>Carter sees the physician-scientist path as uniquely suited to the translational challenge. "When you're a physician, your focus is on treating patients — not on changing the way that patients are treated. And when you're a preclinical researcher, your focus is on identifying new treatments and advancing the field." The physician-scientist, she argues, is trained to do both — and to see that laboratory discoveries actually reach the people who need them."Becoming a physician-scientist is part of my mission to be uniquely trained to advance how patients are treated. And there's nothing really more important to me than that."She also has a message for the next generation. "VCU's program is one of few programs that focus on clinical and translational research, and I would highly recommend it. My experiences with the program have been really positive, and I'd love to see more people, especially students of color, feel safe and feel supported here."Naomi Carter is an M.D.-Ph.D. student in the VCU Medical Scientist Training Program and a former T32 scholar in the Wright Center's Translational Biomedical Sciences Training Program. The TBS program is funded by the National Center for Advancing Translational Sciences (NCATS), grant T32TR004362. For more information, visit <a target="_blank" rel="noopener noreferrer" href="http://cctr.vcu.edu">cctr.vcu.edu</a>.The project described was in part supported by CTSA award No. UM1TR004360 from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health.

Wright Regional Center for Clinical and Translational Science

Photo of Naomi Carter sitting in a black office chair

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Virginia Commonwealth University

Naomi Carter is on a mission to improve how we treat patients. "That is why I wake up every day. It's why I work hard. It's why I mentor. It's why I teach," she says.

Carter is a fourth-year M.D.-Ph.D. student in the Medical Scientist Training Program at Virginia Commonwealth University's School of Medicine and a scholar in the Wright Center's Translational Biomedical Sciences T32 Training Program, a pre-doctoral fellowship funded by the National Center for Advancing Translational Science.

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One Patient at a Time, Mayo Clinic KL2 Scholar Takes on World’s Rarest Diseases

Summary

Article

Mayo Clinic scientists are pushing medicine beyond diagnosis, developing treatments for ultrarare genetic diseases while building a model that could accelerate the path to treatment for many more.