Harnessing GPR17 Biology for Treating Demyelinating Disease

The overarching hypothesis of this project is that GPR17 signaling results in blockade of remyelination in neuroinflammatory lesions. We thus predict that GPR17 could serve as an important target for promoting remyelination in these lesions. The specific aims of this study are: (1) To delineate the role of GPR17 in murine models of demyelinating diseases; and (2) To test the therapeutic potential for GPR17 agonists and antagonists in two models of multiple sclerosis. Our studies conducted during the first year of the project demonstrate that GPR17-deficient mice developed less severe disease and recovered faster from paralysis. Moreover, these mice showed reduced CNS-targeted pathogenic immune responses. These results provide us a strong basis to pursue drug-based treatment for this disease during the next year of the project [as outlined in the original proposal and SOW]. The original document contains color images.