LA JOLLA, CA, September 23, 2009Using clever chemistry, a Scripps Research team has pinpointed the enzyme target of a drug group that stops the progression of the devastating disease Friedreich's ataxia in mice and may do the same for humans. The findings, developed in collaboration with scientists from Repligen Corporation, help advance this treatment approach one step closer toward human clinical trials, which will be a welcome event for disease sufferers who currently have few treatment options.
The work, reported as the cover article of the September 25, 2009 issue of the journal Chemistry & Biology, could also lead to treatments for related conditions such as Huntington's disease and the spinocerebellar ataxias.
"It will be very rewarding if our work actually leads to a therapy for Friedreich's," says Joel Gottesfeld, a professor in the Department of Molecular Biology and leader of the Scripps Research team that discovered the potential treatment. "This is a horrible disease."
Friedreich's ataxia, which afflicts about one of every 20,000 to 50,000 people in the United States, is caused by inadequate production of the protein frataxin, which leads to degeneration of nerve tissue and an array of associated complications including heart disease and scoliosis. In most cases, sufferers are ultimately confined to a wheelchair and many die as young adults.
Researchers have tied this low frataxin production to a large repetition of a specific triplet DNA pattern in the frataxin gene. Though many questions remain open, it appears that the unusual DNA structure resulting from these repetitions somehow attracts enzymes known as histone deacetylases (HDACs). These enzymes alter the packaging of the DNA in chromosomes in a way that inactivates the expression of the frataxin gene, though it remains intact.
In 2006, the Gottesfeld team reported the discovery of a compound simply called 4b that blocked HDAC activity
|Contact: Mika Ono|
Scripps Research Institute