In preclinical models, NDC-1308 activates the production of genes responsible for progenitor cell differentiation, leading to the production of myelin, the protective covering that is damaged in patients with MS. Specific steps include: Progenitor cells (1) mature into pre-oligodendrocytes, (2) which then become pre-myelinating oligodendrocytes, (3) and ultimately, myelinating oligodendrocytes (4).
NDC-1308 is a novel chemical entity, currently in late preclinical development, that is designed to address one of the root causes of MS by inducing oligodendrocyte progenitor cells (OPCs) – the precursors of oligodendrocytes – to mature into oligodendrocytes, the cells that synthesize and maintain the myelin sheath.
Studies in animal models suggest that NDC-1308 significantly induces remyelination of demyelinated nerves by causing a dramatic up regulation of genes in signaling pathways involved in inducing OPC differentiation, leading to myelin sheath production.
Our validation studies, supported in part by a research grant from the National Multiple Sclerosis Society, have reproducibly demonstrated the induction of remyelination in a mouse model of MS in which the neurotoxicant cuprizone was used to remove the myelin sheath from the axons (nerve fibers) of mice.
NDC-1308 is a small molecule that readily crosses the blood-brain barrier, allowing it to reach the tissues in the brain and spinal cord where promoting myelin sheath production is needed. NDC-1308 is being developed for potential use either alone or in combination with other MS therapeutics that currently slow the progression of the disease.