Affiliations: Department of Neurosciences, University of California, San Diego, CA, USA | Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA, USA
Note: [] Correspondence to: Elizabeth A. Thomas, Ph.D., Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, 10550N. Torrey Pines Rd., SP2030, La Jolla, CA, USA. Tel.: +1 858 784 2317;. Fax: +1 858 784 2212; E-mail: [email protected]
Abstract: Background: Deficiencies in brain-derived-neurotrophic-factor have been implicated in the pathogenesis of Huntington's disease (HD). Objective: Glatiramer acetate, an FDA- approved drug used for the treatment of multiple sclerosis, has been shown to increase brain-derived-neurotrophic-factor levels in immune cells; hence, we investigated whether it could have similar effects in striatal cells. Methods: Wild-type and HD striatal cells were treated with glatiramer acetate for 48 hrs. HD transgenic and wild-type mice were injected with glatiramer acetate (1.5 to1.7 mg/mouse) for five days. These treatments were followed by protein measurements for brain-derived-neurotrophic-factor. Results: Glatiramer acetate elicited concentration-dependent increases in brain-derived-neurotrophic-factor protein levels in wild-type and HD striatal cells and in striatal tissue from N171-82Q transgenic mice. Glatiramer acetate also improved metabolic activity of HD striatal cells, and significantly reduced the early hyperactivity phenotype exhibited by N171-82Q transgenic mice. Conclusions: These findings suggest that glatiramer acetate may represent a useful therapeutic approach for HD. The excellent safety and tolerability record of this compound makes it an ideal candidate for drug repurposing efforts.
