J. Paul Taylor, associate member of St. Jude Children’s Research Hospital in Memphis, Tenn., has received an MDA research grant totaling $330,000 over three years. The funds will help support Taylor’s continued research into a number of possible therapeutic targets in spinal-bulbar muscular atrophy (SBMA).
In prior research funded by MDA, Taylor and colleagues developed a fruit fly model of SBMA and used it to determine how mutations in the androgen receptor (AR) gene lead to the death of motor neurons (nerve cells) and deterioration of muscle in this disease.
Specifically, the study team determined that toxicity occurs only when mutant AR enters the cell nucleus and binds to DNA. The team determined that toxicity is mediated by a small interaction surface on AR called "AF2." The team also has determined that toxicity is strongly enhanced by a chemical modification called "sumoylation."
Now, Taylor intends to continue along the same line of study, testing the validity of two therapeutic targets, AF2 and sumoylation, identified in his previous work.
The team will engineer new mouse models of SBMA, some carrying normal forms of AR and others carrying mutant forms of the protein that are defective in DNA binding, incapable of undergoing sumoylation, or have a disrupted or nonfunctional AF2 surface. In parallel, the team will work to identify small molecule inhibitors of these targets in their fruit fly model.
Findings derived from Taylor’s studies could lead to the identification of compounds that can be developed for human clinical testing.
"Funding from MDA has been essential to my research program," Taylor said. "Our previous findings were made possible by MDA, and this new grant from MDA is essential to translating those findings into meaningful therapies."
Funding for this MDA grant began February 1, 2011.