Multiple sclerosis (MS) is the most common demyelinating disease of the CNS, affecting more than 400,000 individuals in the United States and 2.5 million worldwide. MS is classified as an autoimmune disease because immune cells mediate the destruction of the myelin sheath, a covering the not only protects nerve axons, but is also critical for normal nerve impulse conduction. MS commonly presents in young adulthood with transient neurological symptoms, which can progress to a variety of more permanent neurological deficits, including muscle weakness and spasms; difficulties with coordination, balance, and movement; fatigue; acute or chronic pain syndromes; and bladder and bowel difficulties. Many patients also experience impairments in cognitive function, including memory loss, decreased mental processing speed, and diminished executive function. These symptoms can occur early in disease and often worsen with time, even if physical symptoms remain stable.
Two major variants of MS are recognized: relapsing-remitting (RR) and primary progressive (PP), which affects 85% and 10% of MS patients respectively. The former is characterized by transient neurological symptoms with almost complete recovery between relapses, while the latter presents with steadily decreasing neurological function from the time of initial presentation. Nearly 70% of patients with RR-MS will progress to a secondary progressive phase (SP-MS), in which neurological deficits begin to accumulate between relapses.
Although the cause is still unknown, it is widely believed that an unidentified environmental risk in genetically susceptible individuals promotes the aberrant activation of immune cells, including myelin-specific T cells and other innate immune cells. These cells are able to cross the blood brain barrier (BBB), a vascular structure that normally restricts inflammatory cell access to the CNS. Once in the CNS, myelin-specific T cells orchestrate an attack on the myelin sheath. Inflammation in the CNS is particularly devastating because unlike most peripheral cells, neurons and oligodendrocytes (the myelin producing cells) are largely post-mitotic and unable to regenerate.