Public Release: 

Buck researcher makes progress in fight against Huntington's Disease

Buck Institute for Research on Aging

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 disease.

These findings are presented in the June 15 edition of The Journal of Neuroscience in an article titled Calpain Activation in Huntington's Disease. Drs. Ellerby and Juliette Gafni, both of the Buck Institute, are the authors.

"This discovery is an important step forward in our understanding of exactly how Huntington's damages the brain," said Buck Institute President and CEO Dale Bredesen, M.D. "Knowing that calpain plays a key role puts us closer to a treatment for patients of this neurodegenerative disease. Dr. Lisa Ellerby's work may also provide clues for research teams studying the effects of other brain-damaging diseases, such as Parkinson's and Alzheimer's. As a physician, I am heartened to see basic research providing hope for future treatment of patients."

Dr. Ellerby has done Huntington's disease research for the past five years. Because the disease is genetically inherited and therefore caused by one specific mutation in a gene, it can be more readily studied than other neurological disorders such as Alzheimer's and Parkinson's. Advances against Huntington's disease may be directly relevant to other neurological diseases because there are some common patterns in brain damage, such as cleavage of healthy proteins into small, toxic fragments that interrupt normal brain function.


The two-year calpain study was funded by a National Institutes of Health grant. Dr. Ellerby's laboratory also received support from the Huntington's Disease Society of America.

The Buck Institute for Age Research is an independent non-profit research facility. Its mission is to extend the healthy years of each individual's life through clinically relevant biomedical research into the process of aging and the diseases of aging. The Institute is located in Novato, about 30 miles north of San Francisco. For further information, visit our web site at

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