New treatment approaches being studied in multiple sclerosis
Researchers are currently conducting over a thousand clinical trials in multiple sclerosis, investigating different aspects of the disease and new approaches to treatment. The following is a summary of ongoing studies that we hope to hear more about in 2014.
New approaches to treating progressive MS: Current MS therapies typically target key players involved in the inflammatory response, such as T cells or B cells. A novel approach is to target a type of immune cell called the mast cell. Mast cells are best known for being involved in allergic reactions. They release histamine, which causes symptoms such as a stuffy nose or the skin bump after an insect bite. However, there is evidence to suggest that mast cells also promote inflammation in autoimmune disorders such as MS and rheumatoid arthritis (Theoharides and colleagues. Ann N Y Acad Sci 2008;1144:74-82). A new drug in development, masatinib, targets mast cells and has the potential to influence the neurodegenerative processes in progressive MS. A pilot study found that masatinib had a modest effect on disability (Vermersch and colleagues. BMC Neurol 2012;12:36), which has prompted a larger study of the drug. A two-year study is underway in France and preliminary results may be available later this year.
MS vaccine: Perhaps the most personalized of the personalized medicines is Tcelna (imilecleucel-T; formerly Tovaxin), a vaccine that’s developed from an individual’s own cells. After collecting a sample of an individual’s blood, the T cells that damage myelin are isolated, irradiated, and re-injected back into the person’s body. As with other types of vaccines, the body’s immune system detects these cells and attacks them, thereby killing off myelin-reactive T cells. Preliminary results have been encouraging (Loftus and colleagues. Clin Immunol 2009;131:202-215), and the FDA has put Tcelna on the fast track. The Abili-T trial is currently studying Tcelna in people with secondary-progressive MS at 35 sites in the U.S. and Canada.
Targeting Th17: Of the different subtypes of T helper (Th) cells involved in the immune response, Th17 cells are now recognized as being especially aggressive. Th17 cells promote inflammation and tissue damage in the central nervous system in MS by releasing signalling molecules such as interleukin-17 (IL17), first discovered only 20 years ago. IL17 “messages” tell immune cells to invade the CNS and start the process of inflammation. As evidence of the importance of this signalling molecule, the number of IL17-producing cells increases during MS relapses (Durelli and colleagues. Ann Neurol 2009; 65:499-509), and high levels of IL17 can be found in inflammatory plaques in the brains of people with MS (Tzartos and colleagues. Am J Pathol 2008; 172:146-155). A new monoclonal antibody in development is secukinumab (AIN457), which blocks the IL17 inflammatory signal. A preliminary phase II study has reported that secukinumab reduced the development of new inflammatory lesions by 67% (Havrdova and colleagues. ECTRIMS 2013; abstract P520). Additional phase II studies are now underway in MS and other autoimmune disorders, such as rheumatoid arthritis and psoriasis.
Is MS caused by a virus? There has been a great deal of speculation about whether MS is triggered by a virus (see New look at an old virus in multiple sclerosis, MSology, October 24, 2013). So a pilot study called INSPIRE will examine whether treatment with an antiviral drug (raltegravir) normally used to treat HIV/AIDS will have an effect on MS disease activity and progression. A separate study in Switzerland is also investigating whether another drug that targets viruses (called GNbAC1) has an effect in MS.
Are vitamin D supplements worthwhile? The body needs sun exposure to synthesize vitamin D, so most people living in countries far from the equator are deficient in vitamin D, especially during the winter months (see Vitamin D and Multiple Sclerosis, MSology, January 10, 2013). Some studies have suggested that people with MS with lower vitamin D levels have a higher risk of relapses, MRI lesions and disability (Smolders and colleagues. Mult Scler 2008;14:1220-1224; Mowry and colleagues. Ann Neurol 2012;72:234-240; Tremlett and colleagues. Neuroepidemiology 2008;31:271-279). A simple solution would be to take vitamin D supplements in addition to an MS therapy, however, preliminary studies haven’t shown that vitamin D supplements are especially effective (Kampman and colleagues. Mult Scler 2012;18:1144-1151; Mosayebi and colleagues. Immunol Invest 2011;40:627-639; ). Larger studies are needed to know for sure if vitamin D is a useful add-on therapy. The EVIDIMS study is ongoing in Germany and will help to determine if boosting vitamin D levels has a beneficial effect in MS.
Will hormones help? MS generally improves during pregnancy as a result of hormonal changes, which raises the question of whether hormonal therapy might be a useful treatment for women with MS (Robinson & Klein. Horm Behav 2012;62:263-271). Of particular interest is estriol (also called E3), an estrogen that is mostly produced during pregnancy. Preliminary studies have suggested that estriol can reduce inflammatory lesions in women with MS (Soldan and colleagues. J Immunol 2003;171:6267-6274). So estriol is now being studied as an add-on therapy (with Copaxone), and as a possible treatment for cognitive difficulties in MS. This approach may also be good for the gander. A pilot study of testosterone suggested that hormonal therapy may benefit males (Sicotte and colleagues. Arch Neurol 2007;64:683-688), so studies are now underway to see if testosterone supplements improve cognition and fatigue in men with MS.
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