The aim of this project was to identify and characterize drug candidates that induce the repair of the lesions that are associated with multiple sclerosis (MS) disease progression. To achieve this objective, we identified agents that stimulate the regenerative process known as remyelination, which is inhibited during the progressive phases of MS and involves the differentiation of an endogenous stem cell population. Molecules that induce the selective differentiation of this cell type, known as oligodendrocyte precursor cells (OPCs), to oligodendrocytes and thereby lead to remyelination of axons were characterized with respect to their in vitro activity and in vivo efficacy in relevant animal models. This work led to the identification of an approved drug class that was demonstrated to induce in vitro OPC differentiation and enhance remyelination in vivo in multiple relevant rodent disease models. Further, our findings provided rationale for the evaluation of a member of this drug class in a Phase II clinical study at UCSF (ReBUILD), in which partial enhancement of remyelination was observed. Our team is currently working to evaluate the most promising approved drug we have identified, selected based on completed CIRM funded studies, in a Phase IIb clinical trial, as part of a fixed dose combination therapy for the treatment of relapsing-remitting MS.