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

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 to prevent and treat 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.

Researchers led by Mone Zaidi, MD, PhD, MACP, director of the Mount Sinai Bone Program and professor of Medicine at the Icahn School of Medicine at Mount Sinai point out that while obesity and osteoporosis affect hundreds of millions of people worldwide, resources to prevent these diseases remain limited.

FSH was known for years to be an important part of the reproductive system. But 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.

The FSH research builds on a long-term collaboration spanning nearly two decades between Zaidi and Clifford Rosen, MD, a senior scientist at Maine Medical Center Research Institute. Mouse-based data that 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.

“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,” Zaidi says. “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.”