Office of Technology Development (OTD)

Balaraman Kalyanaraman, PhD

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.

Rilutek® does not cure ALS. Rilutek can slow down the progression of the disease but has shown only a moderate increase on survival times.

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.

•    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 

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