Current and Emerging Therapies for Multiple Sclerosis

B. Mark Keegan, MD, FRCP(C)

Recently a patient inquired as to why I had decided to pursue multiple sclerosis (MS) as an area of neurologic subspecialty interest. I told the patient that as a neurology resident, reviewing potential areas of fellowship training, I was quite sure that I wanted to select an area that concentrated on the central rather than the peripheral nervous system. In addition, I also had a strong desire to be involved in an area where there was not only substantial unmet need, but also one where there was considerable promise for further growth within the field. The study of central nervous system (CNS) demyelinating diseases in general, and MS in particular, fit very nicely with these criteria. That early decision has been rewarded in terms of meeting the clinical needs of MS patients in addition to observing tremendous advances in MS evaluation and therapy.

Proven immunomodulatory therapies for relapsing forms of MS now have been available for almost 20 years. Recently, there has been a flurry of activity in the evaluation of further treatments for this inflammatory disease. In this issue of Seminars in Neurology, we will review the clinical evaluation of MS patients, appropriate therapy, and currently available medications as well as medications poised to become available in the near future. The authors of the articles on therapy generally take the outline of describing the history of the therapy, the presumed mechanisms of action, the clinical trials that demonstrate efficacy, the potential side effects of the therapy, and where applicable, its future applications. Dr. Douglas Goodin provides an overview of the traditional injectable therapies of β interferons and glatiramer acetate, which still often constitute first-line treatment for relapsing remitting MS. Dr. Derfuss and colleagues discuss the pros and cons of a highly effective MS medication, natalizumab, where clinical utility has been complicated by its association with progressive multifocal leukoencephalopathy (PML). However, further studies are presented about how to assess and attempt to mitigate the risks associated with this drug.

A new era in oral preparation MS therapy, which has been greatly anticipated, has arisen over the last few years. The first oral MS medication to be approved is fingolimod, a novel medication that modulates sphingosine receptors; this is discussed by Drs. Willis and Cohen. The second oral MS medication approved is teriflunomide, which is discussed by Drs. Oh and O'Connor. Very recently, BG-12 (dimethyl fumarate) was approved for relapsing forms of MS as well and is reviewed by Drs. Phillips and Fox. This medication offers not only efficacy and oral administration, but also has a presumably attractive side-effect profile. Alemtuzumab (Campath 1H) is a novel parenteral MS therapy with a highly robust antiinflammatory profile. Some limitations include treatment-associated autoimmunity to the thyroid and platelets, as discussed by Dr. Alasdair Coles. Progressive forms of MS are where the majority of disability arises in MS. Unfortunately, no medications are reliably effective in stopping or reversing this progression. Dr. Orhun Kantarci discusses the medications that have been proposed and tested in clinical trials. Further efforts in this area will be important in reversing the debility associated with multiple sclerosis.