Specific aims and rationale:
The main aim of this study is to determine the safety of metformin as monotherapy or as an add-on therapy to the disease modifying treatment in aging people with multiple sclerosis (pwMS). While the tolerability of metformin has been studies in the general population, data specific to the MS population is not currently available. Moreover, understanding the gastrointestinal tolerability of metformin when added on MS disease modifying treatment is needed. Secondly, the study aims at understating the potential neuroprotective properties of metformin as measured through magnetic resonance spectroscopy and change in N-acetyl-aspartate (NAA) levels over a 9-month study period. This pilot study will provide valuable insights into the efficacy and safety of add-on or monotherapy metformin therapy as a potential therapeutic approach to address the complex pathophysiology of MS and offer new avenues for promoting neuroprotection along with potential support for neural repair and remyelination in individuals with this debilitating condition. Previous pre-clinical studies have shown that metformin can promote neuroprotection by reducing oxidative stress and inflammation and is able to enhance the reparative mechanisms within the central nervous system (CNS). Currently there are no neuroprotective interventions available for pwMS that directly target the neurodegenerative component of MS, with particular emphasis for the aging MS population. The investigators hypothesize that older pwMS that are treated with metformin will have a significantly lower decline in N-acetylaspartate levels when compared to pwMS not treated with metformin.
