Mount Sinai Researchers Develop a First-in-Class Humanized Antibody Targeting Bone and Fat

Blocking the Follicle-Stimulating Hormone (FSH) whose levels rise at menopause could solve bone loss and weight gain

Senior Author: Mone Zaidi, MD, PhD, MACP, Director of the Mount Sinai Bone Program and Professor of Medicine (Endocrinology, Diabetes and Bone Disease) at the Icahn School of Medicine at Mount Sinai.

Bottom Line: A treatment for obesity and osteoporosis could be on the horizon as Mount Sinai researchers have developed a first-in-class humanized antibody to the follicle-stimulating hormone (FSH) that will reduce body fat, increase bone mass, enhance metabolism, and lower cholesterol. The antibody has the potential of preventing and treating obesity, osteoporosis, and hypercholesterolemia, diseases that affect millions of women and men worldwide. The study provides a framework for clinical testing of the humanized antibody.

Results: Follicle-stimulating hormone (FSH) was known for years to be an important part of the reproductive system. But groundbreaking research 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. In the most recent study, researchers explain the development of a “humanized” monoclonal antibody to block FSH signaling. Furthermore, new evidence was found that blocking FSH also lowers serum cholesterol.

Why the Research Is Interesting:  Obesity and osteoporosis affect nearly 650 million and 200 million people worldwide. Yet the resources for preventing and treating these disorders remains limited, particularly when compared with public health epidemics of similar magnitude. This humanized anti-FSH antibody has the potential of preventing and treating not one, but three diseases—obesity, osteoporosis, and hypercholesterolemia.

Who: It has become increasingly clear that obesity and osteoporosis track together clinically. Women, when they undergo menopause, lose bone and gain body fat. FSH, which rises at menopause, could be responsible for the weight gain and bone loss that many women experience in middle age.

What: The FSH research builds on a long-term collaboration spanning nearly two decades between Dr. Zaidi and Clifford Rosen, MD, senior scientist at Maine Medical Center Research Institute. 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. Mouse-based data that Drs. Zaidi and Rosen concurrently confirmed in each other’s laboratories showed that blocking FSH reduces obesity and increases energy expenditure in both male and female mice fed on a high-fat diet. The most recent study shows the humanization of this FSH-blocking antibody.

Paper Title: First-in-class humanized FSH blocking antibody targets bone and fat

Journal: Proceedings of the National Academy of Sciences

Said Mount Sinai’s Dr. Mone Zaidi:

“This next stage brings us even closer to an effective therapy with an FSH-blocking antibody aimed at preventing and treating both obesity and osteoporosis. Targeting and blocking FSH was found in past studies to be effective in male as well as female mice, so its benefits could extend to both genders in people. What would be fascinating and incredibly rewarding is if we can actually show a significant increase in lifespan while regulating obesity and osteoporosis through a single, FSH-blocking agent.”

To schedule an interview with Dr. Zaidi, please contact Mount Sinai’s Senior Media Specialist, Kathryn Ullman, at [email protected] or at 646-398-2065.

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