MDA awarded Albert La Spada, chief of the division of genetics in the department of pediatrics at the University of California, San Diego, $330,000 to study what causes nerve cells called motor neurons to die in spinal-bulbar muscular atrophy (SBMA) and other neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease) and spinal muscular atrophy (SMA).
La Spada and colleagues have created mouse and motor neuron cell-culture models of SBMA, which results from a genetic flaw in the androgen receptor (AR) gene. Completed studies have led to the identification of candidate pathways that may spur motor neuron degeneration.
Now, La Spada's team will focus on the androgen receptor (AR) protein, which is biochemically modified and made toxic in SBMA. An understanding of the particular proteins, or "enzymes," that catalyze such chemical modifications will set the stage for identification of drug compounds designed to inhibit them.
The team also will work to identify other cell types involved in driving the SBMA disease process. Using a specialized mouse model, the investigators will "turn off" activity of the mutant, or flawed, AR protein in different cell types, starting with motor neurons and muscle cells, in order to determine whether those cells contribute to making motor neurons sick.
"MDA funding has been critical in allowing us to aggressively pursue cutting-edge research approaches in my lab," La Spada said. "Without MDA, there is no way that we could have made all the progress that we did over the last decade."
Findings from the new work may identify targets for the development of therapies to treat SBMA, ALS and SMA.
Funding for this MDA grant began August 1, 2010.