Friedreich's ataxia is a childhood-onset disorder that causes progressive sensory and muscle loss. The molecular mechanisms and processes behind the disorder are still in question, but a Wayne State University School of Medicine researcher is getting closer to the answer.
Timothy Stemmler, Ph.D., associate professor of Biochemistry and Molecular Biology, has studied the cause of Friedrich's ataxia for more than 10 years. His recently published article, "Frataxin and Mitochondrial FeS Cluster Biogenesis," in the Journal of Biological Chemistry, details his comprehensive review of the role that proteins -- which produce small iron and sulfur cluster molecules essential for life -- play in causing Freidreich's ataxia. Dr. Stemmler hopes to develop a strong biochemical understanding of how these proteins function in the cell, which could lead to new alternative treatment strategies aimed at the source of the disorder.
"In their early teens, ataxia patients lose motor ability, they lose the ability to walk and the disorder is often fatal in their early 30s due to complications from heart failure," Dr. Stemmler said. "Because this is all from the inability to make one single protein, I thought it would be an interesting area to look at."
Dr. Stemmler looks at the problem from a biophysical perspective rather than a solely biochemical one, allowing him and his colleagues to apply a variety of biophysical techniques.
At the molecular level, researchers know that ataxia is caused by a deficiency in a mitochondrial protein called frataxin. However, the manner in which the lack of frataxin impairs muscle and neurological function remains unknown.
"If one could figure out what this protein is actually doing in the body, then you can go a long way toward developing treatment strategies that would help patients deal with the disorder," he said.
Dr. Stemmler has studied frataxin proteins in yeast, bacteria, flies and humans, which together indicate that the protein is necessary for the production of iron-sulfur clusters. These clusters perform essential functions, like transferring electrons for cellular respiration, and are involved in the communication between cells and between proteins. When the cell is frataxin-deficient and is unable to produce enough iron-sulfur clusters, the body senses the lack and overloads iron into the cell. The accumulation of iron damages the mitochondria and kills the cell.
"It's this inverted pyramid, where everything hinges on that one point, that one point being not being able to make a single protein," Dr. Stemmler said. "When the cell can't do that the whole iron regulation process collapses."
He hopes his research will apply to other disorders as well, like Parkinson's disease. In both diseases, iron builds up at the base stem of the brain, leading to a loss of nerve function.