Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that has its symptom onset primarily in young and middle-aged adults. Approximately 400,000 Americans are affected by this chronic and disabling disease, with a significant burden placed on the affected person and his or her family, the healthcare system, and society. MS was described as a clinicopathological entity in the mid-19th century, but significant progress in understanding its pathogenesis has been made only in the past few decades. It is now well established that a dysregulated immune system that targets CNS myelinated tissue including brain, spinal cord, and optic nerves causes MS. Inflammation, focal demyelination, and axonal and neuronal loss are prominent features of the pathology. What triggers the autoimmune response is still not understood. However, our understanding of the pathogenesis of MS has led to the development of treatments that alter the course of the disease.
Until 1993 there were no US Food and Drug Administration (FDA)- approved drugs for MS. Recombinant interferon beta 1b (Betaseron®) became the first disease-modifying treatment available for the illness. Since then, five other FDA-approved drugs have become available for MS treatment. These include two forms of recombinant interferon beta 1a (Avonex®, Rebif®), glatiramer acetate (Copaxone®), mitoxantrone (Novantrone®), and natalizumab (Tysabri®). The interferons and glatiramer acetate work by modulating the immune system and lead to upregulation of the anti-inflammatory response and downregulation of the pro-inflammatory response in MS. Mitoxantrone is a chemotherapy agent that kills the T and B cells and temporarily halts the pro-inflammatory response. Natalizumab, a specific monoclonal antibody to alpha 1 integrin molecule (VLA-4), reduces the ability of activated T cells to cross the blood–brain barrier (BBB). All of these medications reduce disease activity in MS, although none is curative. Despite the availability of these six drugs, there remains a significant need for additional drugs for MS. The use of currently available drugs is limited in that all are available only as injections, are expensive, and can cause significant side effects. Therefore, there is considerable interest in the development of safe oral treatments for MS.