Will PEDF Therapy Reverse Chronic Demyelination and Prevent Axon Loss in a Murine Model of Progressive Multiple Sclerosis
Technical Report,30 Sep 2012,29 Sep 2015
University of California - Davis Davis United States
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The purpose of this project was to assess the potential of pigment epithelium-derived factor PEDF as a therapy to enhance central nervous system CNS remyelination and preserve CNS axons in mouse models of multiple sclerosis models. After determining the dosage of recombinant PEDF required to obtain a plateau stimulatory effect on post-lysolecithin CNS remyelination, we demonstrated that intraventricular infusion of recombinant PEDF accelerated CNS oligodendroglial recruitment from both subventricular zone neural progenitor cells and from oligodendroglial progenitor cells OPCs, and accelerated corpus callosum remyelination. We also demonstrated that cuprizone elicited more profound corpus callosum demyelination and slower remyelination in constitutive PEDF knockout mice than in wild-type mice. In chronic experimental autoimmune encephalomyelitis EAE elicited by immunization with a myelin oligodendrocyte glycoprotein MOG peptide, intravenous, but not intraventricular, administration of PEDF diminished severity of neurological deficits.