The Immunomodulatory and Neuroprotective Mechanise of Action of Copaxone, a treatment for Multiple Sclerosis

摘要

Glatiramer acetate manufactured and marketed by Teva Pharmaceuticals Industries, is a complex mixture of synthetic polypeptides with immunomodulatory properties approved for the treatment of multiple sclerosis, including clinically isolated syndrome (CIS) with MRI features suggestive of MS. The current review describes the nonclinical research which has helped define how Glatiramer acetate's possible mechanism of action may affect the immune-mediated inflammation and neuronal damage responsible for MS pathology. Within the immune system, Glatiramer acetate (GA) competes with myelin antigens for binding to MHC class II molecules on APCs inducing a specific shift from pro-inflammatory (Th1/Th17) to anti-inflammatory Th2， and regulatory T cells (Foxp3+Treg). Once activated these GA-reactive Th2 and T reg cells migrate into the CNS, promoting an anti-inflammatory profile within the CNS at the site of multiple sclerosis lesions and halting MS disease pathology. GA treatment results in elevated BDNF levels and increased migration of oligodendrocyte precursor cells to site of neuronal damage, which may be why increased neuronal survival has occurred in patients with MS and EAE models. Glatiramer acetate also appears to affect CD8 and B cells causing them to suppress the