Jody Corey-Bloom1, Haiqun Jia2, Alaina M Aikin2, Elizabeth A Thomas2. 1. Department of Neurosciences, University of California, San Diego, CA, USA. 2. Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.
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 to 1.7 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.
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. HDtransgenic and wild-type mice were injected with glatiramer acetate (1.5 to 1.7 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.
Authors: Steven M Paul; Daniel S Mytelka; Christopher T Dunwiddie; Charles C Persinger; Bernard H Munos; Stacy R Lindborg; Aaron L Schacht Journal: Nat Rev Drug Discov Date: 2010-02-19 Impact factor: 84.694
Authors: C A Altar; N Cai; T Bliven; M Juhasz; J M Conner; A L Acheson; R M Lindsay; S J Wiegand Journal: Nature Date: 1997-10-23 Impact factor: 49.962
Authors: Jody Corey-Bloom; Alaina M Aikin; Ashley M Gutierrez; Jwan S Nadhem; Taylor L Howell; Elizabeth A Thomas Journal: Brain Res Date: 2017-08-18 Impact factor: 3.252