6 August 2002. A mitochondria-protecting, anti-apoptotic bile acid can reduce neurodegeneration and motor deficits in a mouse model of Huntington's disease, according to a report in the current Proceedings of the National Academy of Science. Noting that the compound has proven safe in other FDA-approved uses, the authors suggest it could be used as a therapy for other neurodegenerative disorders as well.
Coauthor Clifford Steer's molecular gastroenterology laboratory at the University of Minnesota in Minneapolis first discovered the anti-apoptotic properties of tauroursodeoxycholic acid (TUDCA). Subsequent work has shown that TUDCA is an antioxidant and that it inhibits mitochondrial processes that might contribute to neurodegeneration. In the present study, conducted with Walter Low, Dirk Keene, and other neuroscientists at Minnesota, TUDCA was administered to the R6/2 transgenic HD mouse, beginning at 6 weeks of age. Compared to untreated Tg mice, the treated mice showed less striatal atrophy, decreased striatal apoptosis and a reduction in abnormal huntingtin protein aggregates. More importantly, locomotor and sensorimotor deficits were significantly improved in the treated mice.
Also important was the fact that these results were achieved with systemic TUDCA, indicating that the compound can cross the blood/brain barrier. Given that TUDCA is produced endogenously and has shown few side-effects in its current uses in gastroenterologic disease, the authors propose that it could have potential in treating other neurodegenerative disorders that involve mitochondrial dysfunction, including Alzheimer's.-Hakon Heimer
Keene CD, Rodrigues CMP, Eich T, Chhabra MS, Steer CJ, Low WC. Tauroursodeoxycholic acid, a bile acid, is neuroprotective in a transgenic animal model of Huntington's disease. PNAS. 6 Aug 2002;99(16):10671-6. Abstract