Professor of Pharmacology
Weill Cornell Medical College
Dr. Szeto's laboratory is involved in the development of peptide drugs that are selectively targeted to the mitochondrial inner membrane and reduce mitochondrial oxidative stress.
Oxidative free radicals are believed to be the underlying cause in aging. Free radicals are produced by the mitochondrial electron transport chain, and they can lead to cell death by oxidation of lipids, proteins, DNA and RNA. Mitochondria are central to the life of the cell, but it is also most vulnerable to free radical damage. Oxidative free radicals can lead to mitochondrial permeability transition and swelling, release of cytochrome c and activation of the caspase cascade resulting in apoptosis. Mitochondrial oxidative stress and dysfunction are implicated in ischemia-reperfusion injury, neurodegenerative diseases, insulin resistance and diabetic complications, atherosclerosis, inflammatory processes and aging.
Dr. Szeto has designed small cell-permeable peptide molecules that target and concentrate >1000-fold in the mitochondrial inner membrane. These peptides are remarkably potent in reducing mitochondrial reactive oxygen species, promote ATP synthesis, and protect against mitochondrial permeability transition, mitochondrial swelling and apoptosis.
Dr. Szeto and her collaborators have demonstrated preclinical efficacy of these mitochondria-targeted peptides in prevention and treatment of myocardial, cerebral and renal ischemia-reperfusion injury, insulin resistance, diabetic complications, neurodegenerative disorders such as Parkinson's Disease and Amyotrophic Lateral Sclerosis, hypertensive heart failure, and muscle wasting associated with mechanical ventilation, thermal burn, and immobilization. The first prototype of these mitochondria-targeted peptides has completed Phase I pharmacokinetics and safety studies in humans and a multi-national Phase II trial for myocardial ischemia-reperfusion injury is scheduled for 2012.