Methods and compositions for treating degenerative and ischemic disorders

Patent metadata

Field	Value
Publication number	US-9399032-B2
Application number	US-201013320348-A
Country	US
Kind code	B2
Filing date	May 14, 2010
Priority date	May 14, 2009
Publication date	Jul 26, 2016
Grant date	Jul 26, 2016

Abstract

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.

First claim

What is claimed is:

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.

2. The method of claim 1 , wherein the cerebral ischemia is a result of a stroke.

3. The method of claim 1 , wherein the S-meclizine is administered in a dose sufficient to produce a serum level of about 1 μM, or a peak serum concentration of at least 1 μM.

4. The method of claim 1 , wherein the S-meclizine is formulated for parenteral administration.

5. The method of claim 1 , wherein the S-meclizine is administered in a daily dose of about 250 to 1000 mg/day.

6. The method of claim 1 , wherein the method reduces organ damage, or the risk of organ damage, resulting from myocardial ischemia.

7. The method of claim 1 , wherein the method reduces organ damage, or the risk of organ damage, resulting from cerebral ischemia.

8. The method of claim 1 , wherein the method reduces organ damage, or the risk of organ damage, resulting from renal ischemia.

9. The method of claim 1 , wherein the S-meclizine is administered for at least several days.

Assignees

• Mootha Vamsi K
• Gohil Vishal
• Sheth Sunil
• Ji Yuhua
• Massachusetts Gen Hospital

Inventors

• Mootha Vamsi K
• Gohil Vishal
• Sheth Sunil
• Ji Yuhua

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P33/02

  Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis · CPC title

• A61P33/00

  Antiparasitic agents · CPC title

• A61P33/06

  Antimalarials · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title