A Small Molecule Induces Oligodendrogenesis Leading to Myelin Sheath Repair


Journal of Clinical Endocrinology & Metabolic Disorders


Steven H Nye, James G Yarger



There is an unmet need for remyelinating therapies to treat demyelinating disorders. NDC-1308 is a small molecule that rapidly crosses the blood brain barrier to drive oligodendrogenesis, a process by which mature, myelinating oligodendrocytes repair damaged myelin sheaths in the central nervous system. NDC-1308 was previously shown to stimulate differentiation of mouse Oligodendrocyte Progenitor Cells (OPCs) in culture by causing a dramatic up-regulation of genes in the pathway for OPC differentiation and myelin synthesis. The present study demonstrates that damaged myelin sheaths found in mice demyelinated with cuprizone can be repaired by treatment with NDC-1308. A chronic NDC-1308 treatment resulted in a 44% and 18% increase in hippocampal and cortical myelination, respectively. In addition, an 18% increase in myelination was measured in the pons. Following NDC-1308 treatment, the OPC pool remained intact, demonstrating that it can serve as a renewable source for sustaining oligodendrogenesis and repair. While NDC-1308 is structurally related to estrogen and it functions through the estrogen receptors, it appears safe for either acute or chronic administration because it is not estrogenic, mutagenic or genotoxic. NDC-1308 is a potential first-in-class remyelinating therapy for repairing the myelin sheath in patients suffering from demyelinating disorders.

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