30 January 2019
“There is no drug for obesity that either works well or is without side-effects,” says US-based endocrinologist, Mone Zaidi, explaining his work on developing an antibody against follicle stimulating hormone (FSH) to treat obesity. Animal studies in mice have been sufficiently encouraging for Zaidi and colleagues to found a start-up company to move the research into human clinical trials.
FSH is produced in males and females, but is most commonly known for its action in stimulating the production and release of the hormone oestrogen in females. A rise in FSH levels during menopause coincides with bone loss, which leads to osteoporosis. Treating osteoporosis is therefore one obvious potential application for anti-FSH antibody therapy. But the hormone’s eﬀect on body fat suggests a possible much wider option to treat obesity in both men and women.
Zaidi, at the Icahn School of Medicine at Mount Sinai, is the leader of an international research team that initially set out to explore the eﬀects of FSH and other hormones on bone. They worked with an antibody that binds to FSH and speciﬁcally blocks its interaction with receptor molecules in cell membranes, discovering that treatment with this antibody increases bone mass in mice.
“Quite serendipitously, we noticed that our data revealed the antibody also dramatically reduced fat levels,” says Zaidi. This effect was at least partly due to increasing the activity of brown fat cells, which are adept at metabolizing fat to release their stored chemical energy as heat. This discovery led the researchers to explore the potential of their antibody in the treatment of both obesity and osteoporosis.
“FSH has very little function in males,” says Zaidi. “So as far as we can tell our procedure is unlikely to have any adverse consequences in men or in post-menopausal women, although caution would be required with pre-menopausal women.” He points out that in tackling obesity, treatment with the antibody could also prevent many of its harmful consequences, including cardiovascular disease, diabetes and cancer.
All such hopes, however, depend on the initial ﬁndings in mice being translated into an eﬀective and safe therapy for humans. This is the challenge that the new company has been set up to tackle. An antibody that is being structurally ‘humanized’ to be compatible with human biology will soon enter toxicology studies then hopefully progress into human clinical trials by 2020.
- Liu, P., Ji, Y., Yuen, T., Rendina-Ruedy, E., DeMambro, V. E. et al. Blocking FSH induces thermogenic adipose tissue and reduces body fat. Nature 546, 107–112 (2017). | article