Multiple sclerosis research – Wikipedia, the free encyclopedia

Posted: November 7, 2013 at 3:40 am

Treatments under investigation for multiple sclerosis may improve function, curtail attacks, or limit the progression of the underlying disease. Many treatments already in clinical trials involve drugs that are used in other diseases or medications that have not been designed specifically for multiple sclerosis. There are also trials involving the combination of drugs that are already in use for multiple sclerosis. Finally, there are also many basic investigations that try to understand better the disease and in the future may help to find new treatments.

Research directions on MS treatments include investigations of MS pathogenesis and heterogeneity; research of more effective, convenient, or tolerable new treatments for RRMS; creation of therapies for the progressive subtypes; neuroprotection strategies; and the search for effective symptomatic treatments.[1]

Advances during the last decades has led to the recent approval of several oral drugs. These drugs are expected to gain in popularity and frequency of use at the expense of previously existing therapies.[2] Further oral drugs are still under investigation, the most notable example being laquinimod, which was announced in August 2012 to be the focus of a third phase III trial after mixed results in the previous ones.[3] Similarly, Other studies are aimed to improve efficacy and ease of use of already existing therapies through the use of novel preparations. Such is the case the PEGylated version of interferon--1a, that has a longer life than normal interferon and therefore it is being studied if given at less frequent doses has a similar efficacy than the existing product.[4][5] Request for approval of peginterferon beta-1a is expected during 2013.[5]

Monoclonal antibodies, which are drugs of the same family as natalizumab, have also raised high levels of interest and research. Alemtuzumab, daclizumab and CD20 monoclonal antibodies such as rituximab, ocrelizumab and ofatumumab have all shown some benefit and are under study as potential treatments for MS.[6] Nevertheless their use has also been accompanied by the appearance of potentially dangerous adverse effects, most importantly opportunistic infections.[2] Related to these investigations is the recent development of a test against JC virus antibodies which might help to predict what patients are at a greater risk of developing progressive multifocal leukoencephalopathy when taking natalizumab.[2] While monoclonal antibodies are probably going to have some role in the treatment of the disease in the future, it is believed that it will be small due to the risks associated to them.[2]

Another research strategy is to evaluate the combined effectiveness of two or more drugs.[7] The main rationale for polytherapy in MS is that the involved treatments target different mechanisms of the disease and therefore their use is not necessarily exclusive.[7] Moreover synergies, in which a drug potentiates the effect of another are also possible. Nevertheless there can also appear important drawbacks such as antagonizing mechanisms of action or potentiation of deleterious secondary effects.[7] While there have been several clinical trials of combined therapy none has shown positive enough effects to merit the consideration as a viable treatment for MS.[7]

Finally, regarding neuroprotective and specially regenerative treatments, such as stem cell therapy, while their research is considered of high importance at the moment they are only a promise of future therapeutic approaches.[8] Likewise, there are not any effective treatments for the progressive variants of the disease. Many of the newest drugs as well as those under development are probably going to be evaluated as therapies for PPMS or SPMS, and their improved effectiveness when compared with previously existing drugs may eventually lead to a positive result in these groups of patients.[2]

The main measure of evolution of symptoms, specially important as an endpoint in MS trials, is the EDSS. However, this and other measures used in clinical studies are far from perfect and suffer from insetiveness or inadequate validation.[9] In this sense there is ongoing research to improve the EDSS and other measures such as the multiple sclerosis functional composite. This is important as the greater efficacy of existing medications force functional measures in clinical trials to be highly sensitive in order to adequately measure disease changes.[9]

Advances in genetic testing techniques have led to a greater understanding of the genetics of MS. However, it is hard to predict how this future discoveries will impact clinical practice or research for new drugs and treatments.[2]

An example of a soon-to-be finished study is the Wellcome Trust case control consortium, a collaboration study including 120,000 genetic samples, of which 8000 are from individuals with MS.[10] This study may presumably identify all the common genetic variants involved in MS.[10] Further studies will probably involve full genome sequencing of large samples, or the study of structural genetic variants such as insertions, deletions or polymorphisms.[10]

Disease-modifying drugs and procedures represent possible interventions able to modify the natural course of the disease instead of targeting the symptoms or the recovery from relapses. Over a dozen clinical trials testing potential therapies are underway, and additional new treatments are being devised and tested in animal models.

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Multiple sclerosis research - Wikipedia, the free encyclopedia

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