Mone Zaidi, MD, PhD, center, with team members in the Department of Medicine (Endocrinology, Medicine and Bone Disease), from left: Sakshi Gera, PhD, Postdoctoral Fellow; Funda Korkmaz, MD, Associate Researcher; Jameel Iqbal, MD, PhD, Senior Faculty; Olena Hadeliya, Associate Researcher; Daria Lizneva, MD, PhD, Instructor; Anisa Gumerova, MD, PhD, Associate Researcher; Alina Rahimova, MD, Biomedical Informatician; Nanette Fraticelli, Grants Coordinator; and Tony Yuen, PhD.  View a video on the FSH project.

Researchers at the Icahn School of Medicine at Mount Sinai have been awarded a $12.5 million grant from the National Institute on Aging for a study seeking to advance the treatment of two public health hazards in older adults—osteoporosis and obesity. The four-part project will focus on follicle-stimulating hormone (FSH), which rises at menopause and could be responsible for the weight gain and bone loss that many women experience in middle age.

FSH was known for years to be an important part of the reproductive system. But the groundbreaking research of Mone Zaidi, MD, PhD, Professor of Medicine (Endocrinology, Diabetes and Bone Disease) at the Icahn School of Medicine at Mount Sinai, and his team showed in a mouse model that FSH also plays a direct role in bone loss and belly-fat gain—and that blocking FSH would reverse those effects. Dr. Zaidi has now developed a “humanized” monoclonal antibody to block FSH signaling, and it will be tested in mice during the new project.

“This next stage will bring us closer to creating an effective therapy with an FSH-blocking antibody aimed at preventing and treating both obesity and osteoporosis,” says Dr. Zaidi, who is principal investigator of the overall project. Targeting and blocking FSH was found in past studies to be effective in male as well as female mice, Dr. Zaidi adds, so its benefits could extend to both genders in people. He will oversee and serve as director for the four new studies, which will be conducted at Mount Sinai and other academic medical centers around the country. Mount Sinai will receive the bulk of the grant—$2 million a year for five years—and will serve as the data center for the project.

The first study, conducted at Mount Sinai, will determine if blocking FSH in mice will change bone mass and body composition across their lifespans, inducing them to live longer. The second study will explore whether the new monoclonal FSH-blocking antibodies can prevent fat gain and bone loss in mice, and if they can also treat existing obesity and osteoporosis. This investigation will be led by Tony Yuen, PhD, Assistant Professor of Medicine (Endocrinology, Diabetes and Bone Disease) at the Icahn School of Medicine at Mount Sinai, and performed collaboratively with UT Southwestern Medical School. For the third study, also in mice, Mount Sinai will team up with Maine Medical Center Research Institute (MMCRI) to study the effects of FSH on bone marrow fat deposits, which are associated with osteoporosis during aging and in menopause. And the fourth project will study the correlation between FSH, body fat, and fracture risk in people from the AGES-Reykjavik cohort of 12,000 women and men between 66 and 93 years of age. This epidemiology project will be led by scientists at the University of California, San Francisco.

The FSH research builds on a long-term collaboration between Dr. Zaidi, director of The Mount Sinai Bone Program, and Clifford Rosen, MD, senior scientist at MMCRI and co-director of the four projects. The results of their previous work were published in the journal Nature in 2017 and were among the eight “notable advances” in biomedicine named that year by Nature Medicine. Dr. Zaidi is hopeful that his team’s work will progress to clinical trials in humans within two years. “What would be fascinating and incredibly rewarding,” he says, “is if we can actually show a significant increase in lifespan while also regulating obesity and osteoporosis through a single, FSH-blocking agent.”