Scientists from Mass General Brigham and the Broad Institute have been studying more effective ways of treating people living with Friedreich’s ataxia (FA). People with this rare and progressive neuromuscular disorder are often diagnosed between the ages of five and 15 and live into their 30s or 40s. A key challenge is that there are no widely approved treatments for the disease, and existing therapies may not be effective in all cases. But that could change thanks to a new study that sheds light on a genetic modifier of the disease, which may open a door to new treatments. Details of the work are available in a new Nature paper titled “Mutations in mitochondrial ferredoxin FDX2 suppress frataxin deficiency.” It describes the investigators’ efforts to use Caenorhabditis elegans (C. elegans) to understand and potentially treat FA. The disease is due to the loss of a mitochondrial protein called frataxin, part of the protein machinery used to make essential co-factors called iron sulfur clusters. These are essential co-factors needed for mediating electron transfer within the mitochondrial respiratory chain among other biological processes. The current findings build on previous work from the laboratory of Vamsi Mootha, MD, an institute member at the Broad Institute and a professor in the departments of systems biology at Harvard Medical School and medicine at Massachusetts General Hospital (MGH). That earlier study showed that hypoxic conditions can partially rescue frataxin loss in human cells, worms, and mice. “In this paper, instead of trying to pursue hypoxia to slow or postpone the disease as a therapy, we simply used it as a trick. We used it as a laboratory tool with which to discover genetic suppressors,” said Joshua Meisel, PhD, lead and co-corresponding author on the current Nature study.…
