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A Novel Therapy for Treatment of Amyotrophic Lateral Sclerosis (ALS)

MCW #1361

 

 Key Inventor

Balaraman Kalyanaraman, PhD

 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.

 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.

 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), MitoTEMPOL treatments delayed disease progression and increased life-span. More significantly, MitoTEMPOL promoted the running activity in G93A mice.

 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 

 Stage of Development

This technology has been tested through in vitro studies and on an ALS mouse model.

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MEDICAL COLLEGE OF WISCONSIN
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Summary Information

Patent Status:
60/716,914

Molecule Type:
Small Molecule

Patent Coverage Type:
Method of Use

Geographical Coverage:
US Patent

Related Areas of Interest:
Central Nervous System 

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