RESEARCH: Bile Acid Inhibits Cell Death in Huntington's disease

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Bile Acid Inhibits Cell Death in Huntington's disease

Source: University of Minnesota

07/29/2002

MINNEAPOLIS / ST. PAUL -- University of Minnesota researchers have found

that a nontoxic bile acid produced in the body prevents apoptosis, or

programmed cell death, in mice with Huntington's disease. This finding, to

be published July 29 in the Proceedings of the National Academy of Sciences

USA (PNAS), may eventually lead to a treatment for Huntington's disease (HD)

in humans. HD is an untreatable neurological disorder caused by selective

and progressive degeneration of neural cells.

In the study, led by Walter Low, Ph.D., professor of neurosurgery in the

university's Medical School, a dose of tauroursodeoxycholic acid (TUDCA) was

administered subcutaneously once every third day for six weeks in mice with

the HD gene. Researchers found TUDCA was able to cross the blood / brain

barrier, something many molecules are unable to do, resulting in decreased

apoptosis in the section of the brain affected by HD and improving the

neurological cell function in the mice.

" We're extremely encouraged by the neuroprotective function of TUDCA in

Huntington's disease and will be examining its potential in future studies, "

said Low.

The bile acid's anti-apoptotic qualities were originally discovered in the

laboratory of Clifford Steer, M.D., co-author of the article and director of

the university's molecular gastroenterology program.

" We determined that this bile acid was unique in its ability to maintain the

integrity of mitochondria, which is so important for normal cell function, "

said Steer. " By so doing, the TUDCA was able to significantly reduce brain

cell death in a variety of conditions, including acute stroke, in rats. We

were interested to see if this would be the case in Huntington's disease as

well. What's exciting about TUDCA, in addition to its remarkable

anti-apoptotic quality, is that it's made in our own bodies and causes

virtually no side effects when given as a drug. TUDCA may even have

potential for treating other chronic neurodegenerative conditions, such as

Parkinson's, Alzheimer's and amyotrophic lateral sclerosis (ALS or Lou

Gehrig's disease). "

Orally administered ursodeoxycholic acid, the parent molecule, is already

FDA-approved for the treatment of primary biliary cirrhosis.