Buck researcher makes progress in fight against Huntington's Disease

Novato, CA -- Scientists at the Buck Institute for Age Research have announced a new understanding of how damage occurs in the brains of Huntington's disease patients. The discovery of a "new player" among harmful proteases advances the fight against Huntington's disease, an inherited neurodegenerative disorder. As it progresses, the disease causes uncontrollable movements, rigidity, dementia and death. The most famous victim of Huntington's disease was American folk singer Woody Guthrie.

Lisa Ellerby, Ph.D., who directs a laboratory at the Buck Institute, suggests that the protease calpain could play an important role in Huntington's disease and therefore be a target for drugs designed to slow or stop the progression of brain damage in the disease. Previous work in the field, including studies conducted by Dr. Ellerby, showed that caspases were involved in Huntington's disease progression. Now, she said, it is clear that "a new player from the calpain family" also is implicated.

A protease is a naturally occurring enzyme, which is responsible for the processing of a protein. Calpains are calcium-modulated proteases. Certain proteases have been implicated in the development of neurodegenerative disorders, either directly by killing neurons or indirectly by cleaving proteins into smaller toxic fragments that threaten the survival of neurons. "Previous work on Huntington's disease showed that calcium dysregulation was involved in pathogenesis, and the calpain discovery ties this knowledge together nicely," Dr. Ellerby said.

"This is not the one cause for Huntington's Disease," she added. "The relationship between calpains and Huntington's disease progression will require further work." Both post-mortem disease tissue and cell culture models were used in the study. Design of calpain inhibitors represents a therapeutic drug target for a number of pharmaceutical companies and therefore may represent a viable treatment strategy for the

Contact: Elizabeth Eshoo
Buck Institute for Age Research

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