Preclinical Proof-of-Principle of MOTS-c and its Role in Metabolic Regulation

MOTS-c is a new mitochondrial-derived peptide hormone that prevents obesity caused by a high-fat diet and stimulates the metabolism in the same way as exercise. The research, "The Mitochondrial-Derived Peptide, MOTS-c, Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance,” was in Cell Metabolism. The CohBar, Inc. company has an exclusive, worldwide license for the development of MOTS-c into therapeutics.

MOTS-c originates in the DNA of mitochondria, commonly known as the ‘powerhouses’ of the cell, which are responsible for converting food into energy. Unlike other hormones, MOTS-c is encoded in the mitochondrial genome. Its major target is muscle where it restores insulin sensitivity, counteracting diet-induced and age-dependent insulin resistance that is a critical feature of type-2 diabetes.Until recently, scientists believed the mitochondrial genome contained only 37 genes and had been relatively unexplored as a focus of drug discovery efforts. Research by CohBar founders and their academic collaborators revealed that the mitochondrial genome has dozens of potential new genes that encode peptides that influence cellular activities by acting as messengers between cells. These peptides have shown disease modifying effects including: metabolic, neuro-protective, cyto-protective and anti-inflammatory, all associated with aging. CohBar’s efforts are focused on optimizing these mitochondrial peptides into drug candidates known as mitochondria-based therapeutics (MBTs). MBTs are being developed for the treatment of diseases associated with aging, such as type 2 diabetes, cancer, atherosclerosis and neurodegenerative disorders.

“This finding is groundbreaking and has the potential to alter the treatment landscape of diseases like diabetes and obesity,” said Dr. Pinchas Cohen, MD, Dean of the USC Davis School of Gerontology, Founder and Director of CohBar and the senior author of the study. “The mitochondrial genome holds enormous potential for identifying and developing a new class of therapeutics, and the discovery of the MOTS-c hormone highlights the role of the mitochondria as an active regulator of the human metabolic system.”