In 2003, we showed that the pituitary glycoprotein thyroid–stimulating hormone (TSH) acts on bone directly, constituting the earliest evidence for any pituitary hormone to function beyond its traditional target1. This represented a paradigm–shift away from the unitary functions of pituitary hormones described in physiology textbooks to the realization that these ancient molecules have highly distributed functions in mammals. In 2006, we likewise reported that follicle–stimulating hormone (FSH), hitherto thought solely to control ovarian function, caused bone loss directly as a potential mechanism for the osteoporosis that was attributed to estrogen deficiency alone2. We further found that the inhibition of FSH action prevented and reversed osteoporosis in mice3. We then went on to show, for the first time, that blocking FSH also causes leanness, which was accompanied by the browning of white adipose tissue and increased energy expenditure4. This paper was selected by Nature Medicine as one of eight “Notable Advances” in biomedicine for 2017 and was featured in New York Times. Yet another serendipitous breakthrough was our more recent finding that blocking FSH prevents the progression of Alzheimer’s disease in mice5. Thus, our studies over the past two decades have unmasked new roles for pituitary hormones of physiologic and medical significance. The studies have also established high FSH as causal to bone loss, obesity and cognitive decline that track together across the transition to menopause––paving the way for treating the three disorders of public health magnitude––namely osteoporosis, obesity and Alzheimer’s disease––simultaneously and with a single FSH inhibitor. To do so, we have developed and characterized a lead therapeutic FSH–blocking antibody6, that is currently under preclinical development.
References: 1Abe et al, Cell, 2003; 2Sun et al, 2006; 3Zhu et al, PNAS, 2012; 4Liu et al, Nature, 2017; 5Xiong et al, Nature, 2022; 6Gera et al, PNAS, 2020.
Mone Zaidi graduated in medicine from King George’s Medical College, India, and trained clinically at the Hammersmith, under the tutelage of Professor Iain MacIntyre, FRS, who discovered calcitonin. After obtaining a PhD, Dr. Zaidi was Lecturer at the Hammersmith and Senior Lecturer and Honorary Consultant at St. George’s Hospital Medical School before being recruited to Mount Sinai School of Medicine as Professor of Medicine and Founding Director of The Mount Sinai Bone Program. He is currently the Mount Sinai Professor of Clinical Medicine and Director of the Center for Translational Medicine and Pharmacology. Zaidi has made groundbreaking discoveries on mechanisms of skeletal homeostasis in health and disease. These studies, spanning over 30 years, included the first description of calcium sensing in the osteoclast and the discovery that locally released nitric oxide acts to suppress bone cells. In 2003, Zaidi’s group published the first evidence for a pituitary–bone axis, a breakthrough in physiology in which pituitary hormones could affect the skeleton directly. In two recent groundbreaking papers in Nature, he found that inhibiting FSH not only increased bone mass, but also reduced body fat and prevented neurodegeneration—in essence, laying a firm foundation for a single anti-FSH agent to treat osteoporosis, obesity and Alzheimer’s disease. This corpus of work was selected by Nature Medicine as one of eight “Notable Advances” in biomedicine for 2017 and was editorialized in the New York Times. Constituting a total of over 450 publications in journals, including Cell, Nature and PNAS, Zaidi’s research has been funded continuously by the NIH. He was elected to the American Society of Clinical Investigation (2000), Association of American Physicians (2004), Interurban Clinical Club of which he is President (2004), the Practitioners’ Society (the oldest medical society in the U.S.) (2016) and the Association of Professors of Medicine (2014). Zaidi was made Master of the American College of Physicians, received the Harrington Scholar–Innovator Award, elected as Fellow of the American Association of Advancement of Science and of the National Academy of Inventors, won the Austrian International Research Prize and the Special Recognition Award from the Association of Professors of Medicine, was bestowed upon with an Honorary Fellowship by the British Pharmacological Society, and is recipient of five honorary doctorates. He was the 2023 Commencement Speaker at the University of Connecticut Graduate School.