February 4, 2005

MIND research study identifies molecule that may help treat Huntington's disease

Using advanced approaches to screening for new drugs, a research team based at the MassGeneral Institute for Neurodegenerative Disease (MIND) has identified a new potential treatment for Huntington's disease (HD), the first such compound not based on an existing medication. The investigators — led by Aleksey Kazantsev, PhD, of MGH Neurology — reported their findings in the Jan. 18 Proceedings of the National Academy of Sciences (PNAS).

A devastating neurodegenerative disorder, HD is one of several conditions in which abnormal repetition of a genetic segment causes mutated proteins to accumulate in the brain in deposits believed to be toxic. The MIND research team used a new yeast-based cellular assay to search for compounds that might inhibit these protein aggregates. The initial screening of their library of 30,000 compounds identified several potential inhibitors, and more selective screens eventually focused on one molecule that powerfully reduced aggregation in the brain cells of a mouse model of HD. The researchers then found that feeding this compound to fruitflies that develop a form of the disorder slowed the neurodegeneration typically visible in insects' eyes.

The MIND team is now preparing to test this compound in mice that develop a form of HD. "These results not only have led us to a potential treatment for HD, they also confirm our vision for MIND — that giving our physician-researchers and basic investigators the most advanced tools and techniques will accelerate the identification of potential drugs and the development of new therapies," says Anne B. Young, MD, PhD, MGH chief of Neurology and a co-author of the PNAS paper. Other MGH co-authors are Deborah Russel and Michele Maxwell, PhD.