Chinese on to something with bear bile, researcher

liver411

Sunday, March 17, 2002 - 12:00 a.m. Pacific Chinese on to something with bear bile, researchers say By Tom Majeski Knight Ridder Newspapers ST. PAUL, Minn. — Gallbladders of black bears have been highly prized by the Chinese for 500 years. Buyers on the black market have paid up to $18,000 for a single gallbladder, believing that the bile inside cures everything from headaches and warts to a lack of sexual prowess. The Chinese are on to something. Researchers at the University of Minnesota have found that a bile acid found in heavy concentrations in black-bear gallbladders can reduce brain damage by more than 50 percent in stroke-impaired laboratory rats. What's more, researchers believe the bile molecule, called tauroursodeoxycholic acid, or TUDCA, also may be beneficial in treating Parkinson's disease, Huntington's disease, Alzheimer's disease, spinal-cord injuries and hemorrhagic strokes. "The beauty of the bile acid is that it doesn't have any side effects," and it also is able to cross the blood-brain barrier, said Dr. Clifford Steer, a professor of medicine, genetics and cell biology and director of the Molecular Gastroenterology Program at the University of Minnesota Medical School. While preliminary results from various TUDCA studies are exciting, Steer said he and his colleagues have been unsuccessful in persuading pharmaceutical companies to fund expensive clinical trials involving human participants. A major reason for their reluctance, he said, is that the patent has expired on the molecule, which reduces the likelihood that research investments would translate into attractive profits. "But with this paper and the Huntington's study coming out, we may get some interest from the private sector," Steer said. "If not, we may go to the (National Institutes of Health) for funding. We are not going to let money stop us from proceeding." While the Chinese use bear bile to treat many conditions, U.S. doctors now use the TUDCA molecule to treat only primary biliary cirrhosis, a liver disease that affects mostly women. The molecule helps control the disease by preserving liver cells. Steer and his colleagues so far have discovered that TUDCA easily crosses the blood-brain barrier, key to treating brain diseases. Because it occurs in extremely small amounts in human gallbladders, the molecule triggers few, if any, side effects. Researchers also have figured out the mechanism that makes the molecule so effective: It protects brain cells by preserving the integrity of the membrane that surrounds mitochondria, which are tiny, organ-like particles floating inside cells that, when injured, trigger cell death. In one of their latest studies, to be published next month in the Journal of Cerebral Blood Flow & Metabolism, Steer and his colleagues mechanically induced strokes in laboratory rats. An hour after the strokes were induced, researchers injected some rats with TUDCA and the rest with a neutral substance. Two days later, the rats were tested for neurological deficits. Some rats from both groups then were euthanized and their brains tested. The rest were euthanized seven days after the study began, and their brains also were analyzed. Among other things, researchers found that rats treated with TUDCA suffered less-serious neurological deficits from their strokes than those in the control group. Brain damage in treated rats also was more than 50 percent less than damage in untreated rats. What's more, the difference was consistent for the entire seven-day period, indicating the cell-protection process was not just a temporary phenomenon. The potential implications from a 50 percent reduction in brain damage are enormous, Steer said. "A 10 percent reduction in damage is the difference between a patient walking out of the hospital or being pushed out in a wheelchair. It's exciting." Steer and his colleagues now want to determine how long it takes for cells to die after a stroke so they know how soon the medication must be delivered to protect brain cells from injury. The research team's next paper, which probably will be published in the May issue of the journal Cell Transplantation, will involved TUDCA's impact on Parkinson's disease. "The results are really quite startling — and very positive, of course," Steer said. In that study, Steer's colleague, Dr. Walter Low, a professor of neurosurgery at the university, found that TUDCA-treated dopamine-producing cells transplanted in the brains of rats had double the survival rate of nontreated cells. Steer and his colleague also are submitting a Huntington's study to a medical journal that shows bile acid protects cells in the area of the brain decimated by the deadly genetic disease. "I can guarantee you it will generate a lot of excitement because there is nothing out there" in the way of treatment, Steer said. The university researchers also are planning to feed TUDCA-laced food to transgenic Alzheimer and Huntington's mice. "By feeding them this stuff from the get-go, can you see a delay in development of their disease? If you can, people will be rushing to take these pills," Steer said. Another promising area of TUDCA research involves spinal-cord injuries. Steer said neurological cell death after a spinal-cord injury is similar to cell death after a stroke, so he's convinced that the bile acid may be beneficial. "Do I think it will work? Absolutely," Steer said. "If you can preserve cell function through this state, you might have a neuron that is alive three weeks later instead of being dead." Copyright © 2002 The Seattle Times Company