Scientific Summary

Cardero’s science therapeutically targets the mitochondria, the principal source of cellular ATP. Chronic depletion of mitochondria has been clearly linked to the progression of muscle failure, or sarcopenia, heart failure, diabetes, and neurodegenerative diseases. Maximum density of mitochondria/cell, and thus the amount of ATP synthesized in each cell, is reached in young adulthood. Progressive loss of mitochondria, particularly in heart and muscle and brain, is associated with the aging process itself and accelerated by obesity, lack of physical activity, and metabolic disorders such as diabetes.

Mitochondria wear out if they are forced to function at excessive rates of activity for sustained periods, as happens to the remaining mitochondria in states of chronic mitochondrial depletion. New mitochondria can be made, in a process termed mitochondrial biogenesis, but this capacity is progressively lost with age or inactivity. The only currently known mechanism to induce mitochondrial biogenesis is physical exercise, which is the basis for exercise conditioning of muscle strength and endurance and cognition, but whose efficacy declines with age.

Progressive muscle failure, or sarcopenia, is particularly associated with mitochondrial dysfunction and depletion. Aberrant contractility associated with muscle disease places excessive metabolic demands on the mitochondria, which become dysfunctional. The end result is mitochondrial depletion, impaired muscle strength, and muscle atrophy.

Our lead clinical program targets the loss of muscle associated with muscular dystrophy. While the gene defect in the muscular dystrophies resides within proteins determining muscle structure, progressive loss of muscle is associated with secondary depletion of mitochondria. The metabolic strain placed on the surviving mitochondria in the progression of muscular dystrophy accelerates the loss of mitochondria due to oxidation injury, abnormal calcium accumulation, and metabolic strain. The loss of mitochondria accelerates the atrophy of the skeletal muscle. A very similar biology occurs within the hearts of patients with muscular dystrophy, causing a high incidence of congestive heart failure.

Cardero Therapeutics has developed data suggesting that enhancing mitochondrial biogenesis is closely associated with improvements in muscle structure and function in both animal models of muscular dystrophy and in the human disease.