Mitochondria play a central role in energy generation in the cell, providing ATP to carry out essential biological functions. As energy output declines, the most energetic tissues are preferentially affected, including the skeletal muscles, heart and retina. Age-related decline in mitochondrial function is associated with numerous chronic degenerative diseases. This talk will describe the discovery of a family of mitochondria-targeted tetrapeptides (SS peptides) that preserve mitochondrial structure and restore cellular bioenergetics by targeting cardiolipin, a unique phospholipid on the inner mitochondrial membrane. Preclinical and clinical development of the first drug candidate (Elamipretide) for rare genetic mitochondrial diseases (myopathy, Leber’s hereditary optic neuropathy, Barth Syndrome) and common age-related mitochondrial diseases (heart failure, macular degeneration, muscle weakness) will be presented.
Dr. Hazel H. Szeto recently left Weill Cornell Medical College where she was Professor of Pharmacology and Director of the Research Program in Mitochondrial Therapeutics. Dr. Szeto pioneered the development of mitochondria-targeted peptides that protect mitochondrial cristae structure and restore cellular bioenergetics by targeting cardiolipin on the inner mitochondrial membrane. Mitochondrial dysfunction and bioenergetics failure is a hallmark of rare genetic diseases and common age-associated chronic diseases. Preclinical studies have demonstrated remarkable efficacy of these compounds in cardiorenal and metabolic diseases, neurodegenerative diseases, skeletal muscle weakness, and neuropathy. These compounds are now in clinical development sponsored by Stealth Biotherapeutics, a company founded by Dr. Szeto in 2006. The first drug candidate (elamipretide) is currently undergoing multiple Phase 2 clinical trials for mitochondrial diseases, heart failure, muscle weakness, and age-related macular degeneration. The US Food & Drug Administration granted Fast Track designation for elamipretide for primary mitochondrial myopathy. Dr. Szeto received her M.D. and Ph.D. (Pharmacology) from Cornell University Medical College.