Harnessing the integrated stress response for the treatment of multiple sclerosis

Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease of the central nervous system (CNS) with no known cure. Though a dozen immunomodulatory therapies exist, their impact on progression of disease appears limited. The field has hence focused on alternate strategies for treatment such as enhancing remyelination and CNS repair. Recent progress has been made on a third complimentary treatment approach that involves protecting oligodendrocytes, and the myelin they generate and maintain, from inflammatory-mediated death via enhancement of the integrated stress response (ISR). Studies in cells and mouse models of MS have demonstrated that the ISR, an innate protective pathway that maintains proteostasis, may be effectively harnessed to aid in the protection of oligodendrocytes and myelin during inflammation. With one ISR-modifying drug already in clinical trial and a number of potential future therapies under investigation, this approach may offer an important component in halting the progression of multiple sclerosis.