Multiple sclerosis (MS) is an autoimmune degenerative disease characterized by motor, sensory, and/or cognitive deficits. These deficits result from demyelination, a process in which the conductive myelin sheath that surrounds axons is compromised, leading to impaired communication between neurons. Normally, oligodendrocyte progenitor cells (OPCs) can differentiate and contribute to myelin formation. However, OPCs present in and around MS lesions appear to exist quiescently and remyelination is limited. While most available MS drugs address the immune component of the disease, effective neuroprotective and restorative agents are lacking. Our proposed research aims to provide proof of principle for a preclinical development candidate that has the potential to drive differentiation of endogenous OPCs to ultimately protect and restore neurons, and improve axon function. This strategy addresses a key unmet medical need in MS by reversing disability and/or preventing disease progression, as is supported by our reproducible preliminary data. Because these data suggest that treatment with this drug stimulates endogenous cells, short-duration dosing regimens will be thoroughly explored. Such a treatment is expected to prevent/improve disability progression by upholding endogenous cells, and the proposed non-continual dosing regimen promises to limit the already intense life style disruption experienced by MS patients
Statement of Benefit to California:
Multiple sclerosis (MS) is a chronic, central nervous system-attacking disease that primarily affects young adults. While MS patients have a virtually normal life expectancy, they suffer from progressive loss of motor and cognitive function, ranging from limb numbness to blindness and paralysis. These symptoms have devastating effects on quality of life, careers, and self-esteem of MS patients and their families. Consequently, economic, social, and medical costs associated with MS are significant. Approximately 800,000 and 450,000 people worldwide and in the US, respectively, are diagnosed with MS. The 160,000 people living with MS in California comprise roughly half the MS patients in the US. Currently, no available MS treatments prevent or reverse underlying progressive degeneration, leaving considerable unmet need for novel, disease-modifying drugs. Our aim is to establish a MS treatment capable of encouraging effective remyelination via stimulation of endogenous oligodendrocyte progenitor cells (OPCs) present in and around MS lesions. Such a drug could be paired with existing immunomodulatory treatments to prevent neurodegeneration and disability progression in MS patients. The development of a treatment that takes advantage of endogenous cells to improve disease will significantly benefit California in many aspects, including cutting the non-negligible MS-associated costs and, most importantly, improving the quality of life of MS patients.