Multiple Sclerosis
An autoimmune disease where the immune system attacks the myelin sheath surrounding nerve fibres in the brain and spinal cord, causing neurological symptoms. Glatiramer acetate is an approved peptide-based immunomodulatory therapy for relapsing forms of multiple sclerosis.
Technical Context
MS pathophysiology: autoreactive T cells (Th1 and Th17) cross the BBB → recognise myelin antigens → inflammatory cascade → demyelination, oligodendrocyte death, and axonal damage → neurological deficits. Types: relapsing-remitting (RRMS, ~85% at onset — discrete attacks with recovery), secondary progressive (SPMS — gradual worsening after initial RRMS), primary progressive (PPMS, ~15% — gradual worsening from onset), and clinically isolated syndrome (CIS — first attack). Glatiramer acetate (Copaxone/generics): 20mg daily or 40mg three-times-weekly SC injection. Mechanism (proposed): GA is a random copolymer of four amino acids (L-Glu, L-Ala, L-Tyr, L-Lys) that mimics myelin basic protein (MBP). It shifts GA-reactive T cells from Th1 (pro-inflammatory) to Th2 (anti-inflammatory) phenotype → these GA-reactive Th2 cells cross-react with myelin antigens in the CNS → local anti-inflammatory cytokine release (IL-4, IL-10, TGF-β) + BDNF secretion → reduced inflammation and potential neuroprotection (bystander suppression). Efficacy: reduces relapse rate by approximately 30% in RRMS.