Huntington's Disease Society of America Announces Latest Research Findings

Huntington's Disease Society of America
Friday, 23 March 2001

New York, NY, March 23, 2001 – In a study funded by the Huntington's Disease Society of America (HDSA) and the National Institute of Neurological Disorders and Stroke (NINDS), among others, leading HDSA researcher Dr. Christopher A. Ross, at Johns Hopkins University, announced that scientists have discovered how the Huntington's Disease (HD) gene attacks and kills cells. The findings of the study appear in the March 23rd issue of the journal Science.

Although the gene for HD was discovered in 1993, the explanation for cell death occurring in the brains of HD patients has remained a mystery. "Our goal has been to understand the mechanism of HD so we can interfere with it early on with drugs," says the study's lead researcher and chair of HDSA's Medical and Scientific Advisory Committee, Christopher A. Ross, M.D., Ph.D. In studies conducted at Johns Hopkins University, researchers have discovered that mutant huntingtin "hijacks" a key molecule termed CBP, which is necessary for activating genes necessary for neuronal survival. "Without CBP, a pathway crucial for cell survival can't get turned on," says Ross. The molecular "hijack" makes direct use of the expanded polyglutamine stretch in huntingtin. "Therefore this mechanism can provide an elegant explanation for the pathology of the whole family of diseases—currently about eight—cause by expanded glutamine stretches in different disease proteins."

"This is a broad advance. It shows us a new way in which genetic errors can cause disease," says neuroscientist Ted M. Dawson, M.D., Ph.D.

In earlier studies when mutant HD was inserted into nerve cells in a culture, the cells died in the same way that brain cells in HD patients die. But in this study, when mutant HD genes were inserted into cultured cells, researchers also added a modified version of the CBP--with the molecular areas that are normally attracted to the mutant huntingtin protein snipped out. "Instead of degenerating, cells in these cultures remained healthy. We were able to rescue them completely," says Ross.

Huntington's Disease is an inherited, degenerative brain disorder that results in the progressive loss of control of both the mind and the body. Each child of an affected parent has a 50% chance of inheriting the disease. Presently, there is no effective treatment or cure for HD.

"We haven't yet demonstrated the turnaround in a live mouse model," says Ross, "which will be one next step in the research. But we have strong evidence from the cell culture experiments that this is an important mechanism. And the molecular events can be set up in a test tube so as to screen for drugs which can block them. Thus we hope our finding will lead directly to therapeutic interventions," said Dr Ross.

Through collaboration between organizations like NINDS and HDSA, HD researchers have made significant advances not only in developing potential treatments for this degenerative brain disorder but also in the way they approach other neurological diseases such as Parkinson's and ALS (Lou Gehrig's disease). "This is exactly why the Huntington's Disease Society of America has allocated $5 million dollars to research this year and why we work so hard to increase research funding each year," says Barbara T. Boyle, National Executive Director/CEO of this national non-profit voluntary health agency. "Reversing cell death brings hope to those affected by HD and we look to Dr. Ross and other HD researchers to develop effective treatments and, ultimately, a cure for this and other neurological diseases."

For more information, or to contact Huntington's Disease Society of America, see their website at: www.hdsa.org