A Novel Therapy for Treatment of Amyotrophic Lateral Sclerosis (ALS)
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State-of-the Art
The current medical treatment for ALS is aimed at maintaining strength and independence, managing symptoms and avoiding complications for as long as possible. Rilutek® is currently the only FDA-approved drug for treating ALS.
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Problem
Rilutek® does not cure ALS. Rilutek can slow down the progression of the disease but has shown only a moderate increase on survival times.
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Solution
Several lines of evidence suggest that ALS is a free radical disease involving mitochondrial energy failure. Increased oxidative damage, protein nitration, apoptosis, and aggregation of proteins are characteristic hallmarks of ALS. It has been previously demonstrated that mitochondria-targeted nitroxides are effective antioxidants and antiapoptotic agents against peroxide-induced apoptosis and oxidative damage in endothelial cells. Dr. Kalyanaraman has developed a method to efficiently couple the nitroxide 4-hydoxy-2,2,6,6-tetramethylpiperidin (Tempol) to the triphenyl phosphonium cation and synthesize a positively-charged Tempol ether at greater yields than previously published methods. When tested on ALS-like transgenic mice (hSOD1-G93A), Mito-Tempol treatments delayed disease progression and increased life-span. More significantly, Mito-Tempol promoted the running activity in G93A mice.
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Benefit
• Targets mitochondrial dysfunction associated with free-radicals
• Demonstrates neuroprotection in mouse ALS model
• Increases life-span in mouse ALS model
• Includes efficient method for synthesizing mitochondrial-targeted Tempol
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Stage of Development
This technology has been tested through in vitro studies and on an ALS mouse model.