Icahn School of Medicine at Mount Sinai Awarded $6 Million NIH Grant to Advance Understanding of Down Syndrome
Researchers from the Icahn School of Medicine at Mount Sinai have been awarded a $6 million grant from the National Institutes of Health (NIH) to advance understanding of how an aging-related hormone known as follicle-stimulating hormone (FSH) may impact early-onset Alzheimer’s disease and co-occurring health conditions in individuals with Down syndrome.
The grant is a Transformative Research Award through the INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) program and the Office of the NIH Director. It is a special type of grant that recognizes high-risk, high-reward projects.
Down syndrome is the most common chromosomal disorder in humans; roughly one in 700 babies is born with the disorder. The genetic alterations of this condition produce enhanced vulnerability to multiple health problems, including bone frailty, obesity, and cognitive impairments, among others. The most devastating condition faced by Down syndrome patients may be Alzheimer’s disease, due to early accumulation of beta-amyloid plaques, a hallmark of the disease.
“Because most people with Down syndrome will develop Alzheimer’s disease dementia, approaches to treat Down syndrome-associated Alzheimer’s disease are particularly needed to improve the lives of both individuals with the condition and their caregivers,” said Ki Goosens, PhD, Associate Professor of Pharmacological Sciences, and Psychiatry, at the Icahn School of Medicine, an investigator in The Friedman Brain Institute, and a Director of the Neurohormone Program in the Institute for Translational Medicine and Pharmacology at Mount Sinai, who will co-lead the study team.
Research suggests that individuals with Down syndrome have elevated levels of FSH from young ages through adulthood. FSH is often studied as a regulator of sexual development and fertility, but published work, mainly from Mone Zaidi, MD, PhD, MACP, Mount Sinai Professor of Clinical Medicine and Director of the Institute for Translational Medicine and Pharmacology, who is also Principal Investigator on the Transformative Research Award, has shown that FSH acts on many tissues beyond the gonads, and has linked age-related increases in FSH to gains in body weight and loss of bone density.
Prior work conducted by Drs. Zaidi and Goosens and other collaborators also established a causal role for age-related increases in FSH and Alzheimer’s pathology.
The Zaidi Laboratory at Mount Sinai recently developed an antibody that blocks the access of FSH to its receptor. This antibody has moved through developability, pharmacokinetic, efficacy, and safety testing and is ready for early-phase clinical trials in Alzheimer’s disease, osteoporosis, and obesity. Through this Transformative Research Award, the Goosens and Zaidi teams will use the antibody to test whether reducing FSH actions improves biological dysfunction in mouse models of Down syndrome.
“This award is truly transformative and clinically meaningful, as it may allow us to tackle the multiple critical morbidities in a relatively common debilitating genetic disorder. Dr. Goosens, a leading neuroscientist, will test our FSH-blocking antibody for the first time in the context of any genetic disease––laying a firm foundation for the wider testing of the FSH antibody as a single drug for Alzheimer’s disease, obesity, and osteoporosis, diseases that affect millions of men and women worldwide,” said Dr. Zaidi.
Preliminary work linking elevated FSH to low bone density and elevated body weight in mouse models of Down syndrome was enabled through the Ram Sundaram and Preethi Krishna Scholar Award to Dr. Goosens through The Friedman Brain Institute Scholars program.
“I am grateful to the generous donors of The Friedman Brain Institute Scholars program. Without this initial funding, we would not have been able to explore our paradigm-shifting hypothesis that a single biological change––early-onset elevated FSH––may underlie both early-onset Alzheimer’s disease and co-occurring disease vulnerabilities in Down syndrome,” said Dr. Goosens. “Now through this Transformative Research Award, our research teams will collaboratively study why FSH is elevated in Down syndrome and investigate whether decreasing the signaling of FSH by the therapeutic antibody reduces Alzheimer’s-like pathology and restores function in other organ systems.”
“We are grateful to the NIH for recognizing the innovative research being performed at The Friedman Brain Institute and at the Institute for Translational Medicine and Pharmacology, and funding the work through a Transformative Research Award,” said Paul J. Kenny, PhD, Ward-Coleman Professor and Chair of the Department of Neuroscience at the Icahn School of Medicine at Mount Sinai and Interim Director of The Friedman Brain Institute. “This funding expands the Icahn School of Medicine’s portfolio for research focused on Down syndrome and may identify a new population that could benefit from treatment with an anti-FSH antibody developed right here at Mount Sinai. This work may open up a completely new therapeutic target that could improve the lives of people with Down syndrome around the world.”
About the Icahn School of Medicine at Mount Sinai
The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the seven member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to New York City’s large and diverse patient population.
The Icahn School of Medicine at Mount Sinai offers highly competitive MD, PhD, MD-PhD, and master’s degree programs, with enrollment of more than 1,200 students. It has the largest graduate medical education program in the country, with more than 2,700 clinical residents and fellows training throughout the Health System. Its Graduate School of Biomedical Sciences offers 13 degree-granting programs, conducts innovative basic and translational research, and trains more than 560 postdoctoral research fellows.
Ranked 11th nationwide in National Institutes of Health (NIH) funding, the Icahn School of Medicine at Mount Sinai is among the 99th percentile in research dollars per investigator according to the Association of American Medical Colleges. More than 4,500 scientists, educators, and clinicians work within and across dozens of academic departments and multidisciplinary institutes with an emphasis on translational research and therapeutics. Through Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai.
-------------------------------------------------------
* Mount Sinai Health System member hospitals: The Mount Sinai Hospital; Mount Sinai Brooklyn; Mount Sinai Morningside; Mount Sinai Queens; Mount Sinai South Nassau; Mount Sinai West; and New York Eye and Ear Infirmary of Mount Sinai.
About the Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with 48,000 employees working across seven hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 9,000 primary and specialty care physicians and 10 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweek’s® “The World’s Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals” and by U.S. News & World Report's® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report® “Best Hospitals” Honor Roll for 2025-2026.
For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Instagram, LinkedIn, X, and YouTube.