Andrew Lieberman, assistant professor of pathology at the University of Michigan Medical School in Ann Arbor, was awarded an MDA research grant totaling $405,000 over three years to study a new therapy approach for spinal-bulbar muscular atrophy (SBMA).
SBMA is an inherited degenerative disorder of lower motor neurons (nerve cells) that is caused by a mutation in the androgen receptor (AR) gene. The mutant protein causes toxicity associated with the male hormone testosterone, resulting in muscle weakness and atrophy in men.
Previous work established that the mutant AR protein is the cause of this toxicity, suggesting that strategies aimed at more efficient degradation of the protein should diminish disease severity.
Lieberman and colleagues found that degradation of the AR protein is tightly controlled by cellular machinery consisting of the heat shock protein 70 (Hsp70).
The investigators now are testing genetic and pharmacologic (drug-related) methods to see whether increasing the stability of Hsp70 will help it more efficiently bind the mutant AR protein and promote its degradation.
“It is our expectation that this work will help define a new therapeutic approach to SBMA and other protein aggregation disorders where degradation of the mutant protein is controlled by Hsp70,” Lieberman said.
Funding for this MDA grant began Aug. 1, 2012.