Latest Research Findings May Yield New Approach for Developing Effective Therapeutics for Huntington's Disease

Huntington's Disease Society of America
Thursday, 14 June 2001

New York, NY, June 14, 2001 – Elena Cattaneo, Ph.D., (University of Milan) a member of the Huntington's Disease Society of America's (HDSA) Coalition for the Cure research group, has uncovered a role for normal huntingtin protein within the brain – to stimulate production of a protein that can protect nerve cells from damage. This significant discovery may lead to the development of effective therapeutics for Huntington's Disease (HD).

HD 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. Currently, there is no effective treatment or cure for the 30,000 Americans and 200,000 who are at-risk to inherit this deadly illness.

HD is caused by the presence of an abnormal mutant huntingtin protein in striatal nerve cells, which causes them to die. However, the nerve cells also possess a normal version of huntingtin protein whose full function in the cell is not yet understood.

Mutant huntingtin protein causes striatal neurons to die, although the precise way that this happens is not yet known, causing the symptoms of Huntington's Disease. Cattaneo's team found that one role played by the normal huntingtin protein is to help regulate the production of BDNF, a protein essential for the survival of striatal nerve cells. This activity was not provided by mutant huntingtin, suggesting that in HD patients the nerve cells have less BDNF to promote their survival.

"Much additional research must be completed before these findings can help patients, and we want to be clear that this is not a cure," says Cattaneo. "But, we're optimistic that our work will help guide the development of new therapies, such as drugs to replace or boost the activity of normal huntingtin, or to increase levels of another brain protein, BDNF."

The basis of Cattaneo's research was to determine how normal huntingtin may protect cultured rat striatal nerve cells from death that is initiated by mutant huntingtin and to test whether neurons sickened by the mutant protein had lost the potential 'protective' pathway.

Through further examination of cultured CNS cells and animal models of HD, Cattaneo's research team revealed that the mutant huntingtin leaves neurons vulnerable to damage as the transcription of the BDNF gene is impaired, resulting in lower levels of this neuron-protecting protein.

Cattaneo speculates that loss of other essential proteins in neurons already sickened by defective gene products may play a role in several other neurodegenerative diseases. The federal government has recently recognized Huntington's Disease as a "model" for other neurodegenerative diseases. The answers we find for HD today may lead to therapies, and ultimately a cure, for Parkinson's, ALS (Lou Gehrig's disease), Alzheimer's and other related diseases.

"The momentum in HD research continues to accelerate and we are very hopeful that effective therapies, and ultimately a cure, for Huntington's Disease are well within our reach," says Barbara Boyle, National Executive Director/CEO, HDSA.

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