Methods and compositions for treating degenerative and ischemic disorders

摘要

Model systems have shown that shifting a cell's reliance from oxidative phosphorylation (OXPHOS) to glycolysis can protect against cell death. Exploiting the therapeutic potential of this strategy, however, has been limited by the lack of clinically safe agents that remodel energy metabolism. The present invention identifies non-toxic small molecules (e.g., drug-like compounds) that are capable of modulating oxidative metabolism. One identified compound comprises meclizine. As described herein, meclizine, and its enantiomer S-meclizine, redirects OXPHOS to glycolysis. Such compounds could be protective or therapeutic in degenerative disorders such as diabetes, Huntington's, Parkinson's, and Alzheimer's disease and/or ischemic disorders including, but not limited to, stroke, heart attack, or reperfusion injuries.

主权项

1. A method for reducing organ damage, or the risk of organ damage, resulting from myocardial ischemia, cerebral ischemia, or renal ischemia, the method comprising administering a therapeutically effective amount of an S-enantiomer of meclizine, substantially free of the R-enantiomer of meclizine, to a subject in need thereof.