Study indicates promise in Huntington's treatment

"This study supports the hypothesis that CoQ exerts antioxidant effects in patients with Huntington's disease and therefore is a treatment that warrants further study," says University of Rochester Medical Center neurologist Kevin M. Biglan, M.D., M.P.H., lead author of the study. "As importantly, it has provided us with a new method to evaluate the efficacy of potential new treatments."

Huntington's disease (HD) is a genetic, progressive neurodegenerative disorder that impacts movement, behavior, cognition, and generally results in death within 20 years of the disease's onset. While the precise causes and mechanism of the disease are not completely understood, scientists believe that one of the important triggers of the disease is a genetic "stutter" which produces abnormal protein deposits in brain cells. It is believed that these deposits -- through a chain of molecular events -- inhibit the cell's ability to meet its energy demands resulting in oxidative stress and, ultimately, cellular death.

Scientists had previously identified the correlation between a specific fragment of genetic code, called 8-hydroxy-2'-deoxyguanosine (80HdG) and the presence of oxidative stress in brain cells. 80HdG can be detected in a person's blood, meaning that it could serve as a convenient and accessible biomarker for the disease. Researchers have also been evaluating the compound Coenzyme Q10 as a possible treatment for HD because of its ability to support the function of mitochondria -- the tiny power plants the provide cells with energy -- and counter oxidative stress.

The study's authors evaluated a series of blood samples of 20 individuals with HD who had previously undergone treatment with CoQ in clinical trial titled Pre-2Care. While these studies showed that CoQ alleviated some symptoms of the disease, it was not known what impact -- if any -- the treatment had at the molecular level in the brain. Upon analysis, the authors found that 80HdG levels dropped by 20 percent in individuals who had been treated with CoQ.

CoQ is currently being evaluated in a Phase 3 clinical trial, which is the largest therapeutic clinical study to date for HD. The trial -- called 2Care -- is being run by the Huntington Study Group, an international networks or investigators.

"Identifying treatments that slow the progression or delay the onset of Huntington's disease is a major focus of the medical community," said Biglan. "This study demonstrates that 80HdG could be an ideal marker to identify the presence oxidative injury and whether or not treatment is having an impact."

Additional co-authors include Karl Kieburtz, M.D., M.P.H. and Ryan Evans M.D. with URMC, Ray Dorsey, M.D. with Johns Hopkins University, Steven Hersch, M.D., Ph.D. with Massachusetts General Hospital, and Ira Shoulson, M.D. with Georgetown University. The study was supported by grants from the National Institutes of Health. Funding for the original Pre-2Care study was provided by the CHDI Foundation.