MINNEAPOLIS / ST. PAUL (July 24, 2002)

University of Minnesota researchers have found that a non-toxic bile acid produced in the body prevents apoptosis, or programmed cell death, in mice with Huntington's disease. This finding, published July 29 in the Proceedings of the National Academy of Sciences USA (PNAS), may eventually lead to a treatment for Huntington disease (HD) in humans.

In the study, led by Walter Low, Ph.D., professor of neurosurgery in the university's edical School, a dose of tauroursodeoxycholic acid (TUDCA) was administered under the skin 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. This resulted in a decrease in apoptosis in the section of the brain affected by HD, improving the neurological cell function in the mice.

"We're extremely encouraged by the neuroprotective function of TUDCA in Huntington 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 [the power generators of a cell], 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 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.

Other authors of the study include C. Dirk Keene, Cecilia M.P. Rodrigues, Tacjana Eich, and Manik S. Chhabra.

Can you translate that for me?

Apoptosis is a process that cells use to self-destruct if they are damaged or can no longer work properly. In the brain of a person with HD, mutant huntingtin (produced by the mutant gene that causes HD) creates toxic lumps of the mutant huntingtin protein in brain cells, and causes the cells to start the process of apoptosis - the cell's self-destruct sequence.

In this study, researchers gave HD mice a chemical - tauroursodeoxycholic acid (TUDCA) - that could successfully enter the brain and slow down the process of apoptosis that is started by the mutant huntingtin. By slowing down apoptosis - the brain cell's self-destruct sequence - researchers were able to extend the lives of mice with HD.

This is an extremely positive finding since TUDCA is already produced by the human body. If it is eventually shown to be effective in other models (including humans), there would be almost no side-effects for a person taking the chemical as a drug. -SM