Project 467149

Multiple sclerosis (MS) is a progressive inflammatory autoimmune disease and is now increasingly considered to be a metabolic disease. In individuals with MS, the immune system attacks the protective myelin sheath of the central nervous system (CNS), leading to a variety of neurological deficits. Long-term regenerative interventions are urgently required for improved quality of life of MS patients. These interventions would likely include promoting re-myelination through mature oligodendrocytes - a type of glial cell which aids in myelination of the CNS. Oligodendrocyte precursor cells (OPCs) are engaged at MS lesion sites but are unable to differentiate into mature oligodendrocyte cells due to neuroinflammation present at the lesion site. Monoacylglycerol lipase (Mgll) has been identified as a target for MS treatment, since repression of Mgll in animal models and MS patients has been found to promote OPC maturation. Metformin, an FDA- approved drug typically used in treatment of type II diabetes mellitus (DMII), has been demonstrated in animal models to repress Mgll expression, thus enhance OPC maturation, as well as reverse social cognition impairment. No research thus far has examined the impact of metformin on traditional measures of social cognition, in individuals with MS. The purpose of our investigation is to evaluate the impact of metformin treatment and Mgll levels on social cognition in individuals with MS and co-morbid diabetes by comparing participants treated with metformin with those who are not taking metformin. If metformin is associated with re-myelination and higher social cognition in those with MS, then future clinical trials can use Mgll levels as a biomarker for metformin treatment to promote CNS re-myelination and improve social cognition.