The results of the research are being published on August 20 in an advanced, online version of the journal Nature Chemical Biology.
In the new study, the researchers tested a variety of compounds that inhibited a class of enzymes known as histone deacetylases in a cell line derived from blood cells from a Fredreich's ataxia sufferer. One of these inhibitors had the effect of reactivating the frataxin gene, which is silenced in those with the disease. The researchers then went on to improve on this molecule by synthesis of novel derivatives, identifying compounds that would reactivate the frataxin gene in blood cells taken from 13 Friedreich's ataxia patients.
In fact, one of the compounds the researchers tested produced what amounted to full reactivation of the frataxin gene in 100 percent of cells tested.
"This is marvelous," said Joel Gottesfeld, Ph.D., a professor in the Scripps Research Department of Molecular Biology and leader of the project. "I've met the parents of many children affected with the disease and some of the patients and it would be just a dream to be able to help them."
"Dr. Gottesfeld's work holds tremendous promise of real therapeutic benefit for Friedreich's ataxia patients," said Ron Bartek, president of Friedreich's Ataxia Research Alliance (FARA). "This discovery appears to be our only near-term prospect for significantly increasing transcription of the frataxin gene. FARA is pleased to have been able to support this important work."
Friedreich's Ataxia, a Debilitating Disease
About one of every 20,000 to 50,000 people in the United States has Friedreich's ataxia, which is caused by a genetic defect that prevents adequate production of the protein frataxin. In neuronal and muscle cells, frataxin is essential for proper functioning of mitochondria, the energy producers for cells. Low levels of the protein lead to degeneration of nerve tissue in the spinal cord and nerve
Contact: Keith McKeown
Scripps Research Institute