Conventional Therapies

IFN-beta (IFN-b) (e.g., IFNA-beta-lb, Betaseron; IFN-beta-la, Avonex; and IFN-beta-la, Rebif)17 is used to modify the immune response in MS. IFN-beta affects the immune system by inhibiting T-cell stimulation and increasing the activity of CD8 suppressor lymphocytes. IFN-beta also regulates the production of IFN-gamma. The net effect is to reduce the overall immune response to myelin in MS. Also, IFN-beta restores the integrity of the blood-brain barrier, decreasing T-cell migration into the brain. In inflammatory conditions in the CNS such as multiple sclerosis or experimental autoimmune encephalomyelitis (EAE), circulating lymphocytes and monocytes=macrophages readily cross the blood-brain barrier and gain access to the CNS leading to edema, inflammation, and demyelination. Also often used to modify the disease process in MS is glatiramer acetate, a mixture of synthetic polypeptides composed of four amino acids, and based on the structure of MBP, which is believed to inhibit the T-cell response to multiple antigens in myelin. Glatiramer acetate induces T-regulatory cells known as GA-specific regulatory CD4 and CD8 lymphocytes, as well as causing a shift from Th1 to Th2 activity, increasing the secretion of anti-inflammatory cytokines and suppressing the autoimmunity led by Th1 cells.18

Free radicals are believed to play a role in the pathogenesis of multiple sclerosis.

When IFNs and glatiramer acetate do not effectively control MS, immunosuppressant drugs are often used. The most commonly used such agents are azathioprine, cyclophosphamide, methotrexate, and mitoxantrone. Mitoxantrone (Novantrone) is often used to reduce neurologic disability and=or the frequency of clinical relapses in secondary progressive, progressive-relapsing, and worsening relapsing-remitting MS. This agent acts by suppressing lymphocyte production in bone marrow, decreasing T-cell and B-cell numbers.19

High-dose corticosteroids are used to manage acute relapses. Intravenous methylpredniso-lone is the standard treatment for MS relapses and elicits rapid reduction of gadolinium enhancing (Gd ) lesions seen on brain MRIsof patients with MS.20 Natalizumab (Tysabri) is a recombinant humanized anti-a-4 integrin monoclonal antibody approved for use in relapsing-remitting MS patients. It decreases leukocyte migration from peripheral blood into the CNS.21


Research has found that higher serum levels of 25-hydroxyvitamin D are associated with a decreased risk of developing MS,22 and animal models of the disease indicate that supplementation with vitamin D reduces the frequency of MS and retards its progression. A study of vitamin D supplementation showed it to be associated with a 40% reduction in MS risk,23 and another study found a strong association between reduced exposure to sunlight, decreased vitamin D levels, and greater disability in persons with MS.24 It has also been found that vitamin D levels are lower during relapses of MS than during remission periods, suggesting a possible role of vitamin D on the course of the disease,25 and the finding that concentrations of 25-hydroxyvitamin D are lower and those of intact parathyroid hormone are higher during relapses than during remissions suggests that altered calcium metabolism may also play a role in the course of MS.26

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