The Dynamic Landscape of MS Treatement

The current landscape in the treatment of MS is dynamic and continually changing. In the future, neurologists will use immunomodulator agents, which work gradually to alter the immune system to be in a less inflammatory state in conjunction with immunosuppressive medications. The long-term safety of immunomodulator agents is established in contrast to that of immunosuppressive agents, which work immediately on the immune system, but also may lead to blood dyscrasias and infection due to their more potent and immediate effects. A number of new treatments are currently under investigation for MS. Ironically, even something as simple as vitamin D supplementation may be helpful.


Emerging Therapies Under Investigation for Multiple Sclerosis

A number of studies are underway on investigational drugs for MS.
Oral Drugs

Cladribine. The oral drug closest to approval may be oral cladribine. Cladribine is a purine nucleoside analog, and it interferes with the proliferation of lymphocytes.


Fingolimod or FTY720. Fingolimod works by causing the sequestration of T cells in lymph nodes. On the basis of recently published results, it was found that during the initial 6 months of treatment, once daily fingolimod reduced the rate of inflammatory disease activity, measured by Gd-enhanced MRI, by up to 80% compared with placebo and reduced the rate of clinical relapses by more than 50%.[11]


Teriflunomide. Teriflunomide, a dihydroorotate dehydrogenase inhibitor, has immunomodulatory effects, including the ability to suppress experimental allergic encephalomyelitis. In a phase 2 study, the drug showed significant benefit on MRI T2 burden of disease and slight benefit (not statistically significant) in relapse rate.[12]


BG00012 (oral fumarate). A multicenter, phase 2, controlled clinical trial of oral BG00012 (an oral fumarate) led to a 69% reduction in active inflammation on MRI scans in 257 people with relapsing-remitting MS.[13] The agent was originally tested in psoriasis.


Laquinimod. Laquinimod is a novel synthetic immunomodulator compound. It has demonstrated therapeutic efficacy in both acute and chronic experimental autoimmune encephalomyelitis models and in nonclinical models of other autoimmune diseases, such as rheumatoid arthritis and insulin-dependent diabetes. The drug had benefit on MRI active lesions, but no significant effect on relapses in a phase 2 study.[14]
Other Therapies

Several nonoral therapies are also under development. MBP 8928 is a peptide sequence from myelin basic protein that has maximal interaction with T cells and can induce immune tolerance to myelin in patients who have the HLA-DR2 haplotype (20% to 30% of the general population). It is administered intravenously every 6 months. In 1 study, the drug was shown to safely reduce progression of disease over 5 years in chronic progressive MS patients.[15]


A promising group of molecules, the CCR2 antagonists, block a major chemokine receptor pathway required for the attraction of monocytes from the bloodstream into sites of inflammation. Once at the site, monocytes then differentiate into inflammatory macrophages. Macrophages are an important part of the inflammatory process in MS. CCR2 antagonists are currently being investigated in MS.[16]



Investigators found that the risk of developing MS decreased with increasing serum levels of 25-hydroxyvitamin D, a form of the vitamin that reflects recent exposure to sunlight. (Most vitamin D within the body comes from exposure to ultraviolet light, rather than from foods.) This apparent protective effect of vitamin D was found to be statistically significant only in the study population that had the highest levels of vitamin D and only in whites, not in blacks or Hispanics. A recent study found that MS risk was lowest among those with the highest levels of vitamin D (defined as 99.2-152.9 nmol/L) and highest among those with the lowest levels of vitamin D (defined as 15.2-63.2 nmol/L).[18] Earlier studies suggested that vitamin D may show benefit in MS prevention.

Source : http://www.medscape.com/viewarticle/555334?src=mp