Wayne State Prof Gets Closer To Cause Of Childhood Disease
Friedreich's ataxia is a childhood-onset disorder that causes progressive sensory and muscle loss. The molecular mechanisms and processes behind the incurable disorder are still in question, but a Wayne State University researcher is getting closer to the answer.
Timothy L. Stemmler, associate professor of biochemistry and molecular biology in WSU's School of Medicine, has studied the causality of Friedriech's ataxia for more than 10 years and recently had an article published in the Journal of Biological Chemistry.
In it, the comprehensively reviewed the role that proteins, which produce small iron and sulfur cluster molecules essential for life, play in causing Friedreich's ataxia. Stemmler hopes to develop a strong biochemical understanding of how these proteins function in the cell and this will lead to new alternative treatment strategies aimed at the source of Friedreich's ataxia, in contrast to currently available treatments that can only target the disorder's effects.
"In their early teens, ataxia patients lose motor ability, they lose the ability to walk, and the disorder is often fatal in their early thirties due to complications from heart failure," said Stemmler. "Because this is all from the inability to make one single protein, I thought it would be an interesting area to look at."
Stemmler looks at the issue with a biophysical perspective rather than a solely biochemical one, allowing him and his colleagues working with him in his laboratory to apply a wide variety of biophysical techniques.
At the molecular level, it is known that ataxia is caused by a deficiency in a mitochondrial protein called frataxin, but the exact way in which not producing frataxin impairs muscle and neurological function remains unknown. Investigating this is a major focus of Stemmler's research.
"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," said Stemmler.
Stemmler has studied frataxin proteins present 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.
But when the cell is frataxin-deficient and is unable to produce enough iron-sulfur clusters, the body senses a lack of iron-sulfur clusters 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," said Stemmler. "When the cell can't do that, the whole iron regulation process collapses."
Stemmler also hopes that 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, which leads to a loss of nerve function.
"I think the potential to solve this problem is great. So that's why we do it," said Stemmler.
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