Study identifies trigger for Huntington's disease

By Will Dunham

WASHINGTON, April 22 (Reuters) - A mistake in the way the body's cells repair their DNA may trigger onset of Huntington's disease, researchers said in a finding they hope leads to better treatment of the incurable hereditary brain disease.

Writing on Sunday in the journal Nature, the researchers said their study involving mice explains the mechanism for how Huntington's disease begins and how it becomes worse over time in people who have inherited the gene that causes it.

Scientists knew a version of a gene called "huntingtin" caused the disease, which makes brain nerve cells waste away. But they had wondered what spurred its onset, usually in middle age.

A segment of the gene grows when cells try to remove lesions caused by a process called oxidation. This happens to DNA constantly in the body and usually cells can repair themselves.

With Huntington's, normal DNA repair enzymes keep these lesions in check at first but over time the growing numbers of lesions overwhelm the repair system, said Cynthia McMurray, a professor of pharmacology at the Mayo Clinic in Rochester, Minnesota.

"The key finding is that damage to the DNA and its normal repair is actually causing mutation leading to disease," McMurray said in a telephone interview.

"Nobody has connected the dots before," McMurray said a statement.

Huntington's is marked by degeneration of nerve cells in certain areas of the brain that causes uncontrolled movements, balance problems, loss of intellectual faculties and emotional disturbance. The disease, which affects an estimated 30,000 people in the United States alone, eventually can make a person unable to walk, talk or swallow.

"Oxidative damage has been linked to aging and neurodegenerative disease for decades," McMurray said. "But nobody has really understood how oxidation can lead to genetic problems during aging. And this study links the oxygen damage directly to a causative event that can cause neuronal death."

The researchers hope the findings can guide development of drugs that might stop or slow the onset of the disease. McMurray said an important step is to find a drug that inhibits a key enzyme involved in the process.

The study involved genetically engineered mice with a version of the human huntingtin gene. It was conducted by Mayo Clinic researchers and collaborators from the U.S. National Institutes of Health and the University of Oslo in Norway.

((Reporting by Will Dunham, editing by Maggie Fox and Bill Trott; Reuters Messaging: will.dunham.reuters.com@reuters.net)) Keywords: HUNTINGTONS GENETIC

(C) Reuters 2007. All rights reserved. Republication or redistribution ofReuters content, including by caching, framing or similar means, is expresslyprohibited without the prior written consent of Reuters. Reuters and the Reuterssphere logo are registered trademarks and trademarks of the Reuters group ofcompanies around the world.nN20319695