Natl. Academy of Sciences Reports on Promising HD Research
Huntington's Study Looks Promising
By PAUL RECER AP Science Writer July 29, 2002, 5:55PM EDT
WASHINGTON - A bile acid the body produces in small amounts is able in laboratory studies to slow the progress of Huntington's disease, a fatal, inherited brain disorder that destroys the mind and has affected about 30,000 Americans.
"We found in mouse studies that this compound protects the animals' neurons (brain cells) from the effects of the Huntington's disease gene," said C. Dirk Keene, first author of a study appearing this week in the Proceedings of the National Academy of Sciences.
Keene, a researcher at the University of Minnesota, said many more laboratory studies are needed before the drug could be considered for testing in humans, but he said the research is important because it offers the hint of a future treatment for a lethal disorder that now has no treatment.
"We hope it will be as effective in humans as it seems to be in rodents," Keene said.
"It is an interesting finding that needs to be followed up," said Dr. James F. Gusella, a Huntington's disease researcher at Massachusetts General Hospital and the Harvard Medical School. But he cautioned that although animal research provides clues about Huntington's, "They are still quite distant from being able to treat human patients."
Huntington's disease, or HD, is caused by a single defective gene that is inherited. About one in every 10,000 babies worldwide is born with the gene mutation and about 30,000 Americans have been diagnosed with HD.
The disease causes a progressive loss of neurons in the brain, leading to changes in personality, mood and judgment. As the disease progresses, patients develop slurred speech, an unsteady walk and difficulty in swallowing. Symptoms can appear as early as age 2 or as late as age 70 and will lead to death in 10 to 25 years.
Researchers discovered the gene that causes Huntington's in 1993, but there are still no approved drugs or treatments to slow its progression.
In the study, Keene and his co-authors used a type of mouse, called R6/2, that was developed to have a part of the flawed HD gene and to develop symptoms of the disorder.
For comparison, the researchers also tested a group of mice with normal genes.
Starting at about six weeks of age, half of the R6/2 mice were injected with a compound called tauroursodeoxycholic acid, or TUDCA. Earlier studies had shown that TUDCA, a type of bile acid, tended to block cell death. The new study was designed to see if it would prevent the HD-caused death of brain cells.
At 10 weeks, the two groups of R6/2 mice and the normal mice were tested in a maze and on a treadmill. Keene said TUDCA-treated mice could perform up to 50 percent better on the tests than the R6/2 mice not given TUDCA.
"The treated animals were no different than the ... non-Huntington's disease animals," said Keene.
An examination of the animals' brains after 13 weeks showed that TUDCA-treated mice had significantly fewer dead neurons than the R6/2 mice not given TUDCA.
Keene said researchers now want to start the TUDCA treatments on R6/2 mice at an earlier age to see if it can extend their life. The mice usually die of HD symptoms at about 14 weeks. He said it is believed that HD starts killing brain cells long before symptoms of the disorder appear.
The flawed gene that marks HD can now be detected before birth. If a drug can be found that prevents the death of brain cells starting at an early age, it may be possible to control the disorder throughout life, said Keene.
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