Review New treatment strategies in multiple sclerosis Joanne L. Jones ⁎, Alasdair J. Coles Dept. of Clinical Neurosciences, Box 165 Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK abstract article info Article history: Received 8 March 2010 Revised 27 May 2010 Accepted 7 June 2010 Available online xxxx Multiple sclerosis is the most common, non-traumatic, disabling neurological disease of young adults, affecting an estimated two million people worldwide. At onset multiple sclerosis can be categorised clinically into relapsing remitting MS (RRMS — 85–90% of patients) or primary progressive MS (PPMS). Relapses typically present sub-acutely over hours to days with neurological symptoms persisting for days to weeks before they gradually dissipate. At first full recovery is the norm, later patients accumulate deficits and ultimately most convert to a secondary progressive phase (SPMS), characterised by deficits that increase in the absence of further relapses. The clinical picture reflects the complex interplay of focal inflammation, demyelination and axonal degeneration occurring within the central nervous system. Since the introduction of a genuine disease-modifying drug, interferon-beta1b in 1993, there has been a growing interest from academia and pharmaceutical companies alike in multiple sclerosis therapy. In part this effort has focused on investigating the “window of therapeutic opportunity” within the natural history of the disease: it is becoming increasingly clear that immunotherapies are not useful in the secondary phase of the disease but may offer long-term benefit if given early in the relapsing–remitting phase. In part, attention is being paid to the details of dosing and administration of the various licensed therapies, but there is also a significant research effort to explore new ways to treat the disease. In this review, we first sketch the landscape of novel therapies in multiple sclerosis and then discuss in detail approaches which are likely to emerge over the next few years. © 2010 Elsevier Inc. All rights reserved. Contents The landscape of novel therapies in multiple sclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 New and emerging therapies and the rationale behind their use. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Lymphocyte migration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Natalizumab . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Fingolimod (FTY720) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Targeting T cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Daclizumab . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Targeting B cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Rituximab . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Mixed targets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Alemtuzumab . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Cladribine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 In conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 The landscape of novel therapies in multiple sclerosis Broadly speaking, novel therapies of multiple sclerosis aim to either disable a component of the immune system or to prevent neurodegeneration, as seen in progressive forms of the disease. Disabling the immune system can be achieved in a number of ways, including: i) targeting whole populations of immune cells believed to be involved in disease pathogenesis (e.g. daclizumab neutralising the CD25 molecule on all T cells), ii) blocking the migration of peripheral lymphocytes in to the CNS (natalizumab and fingolimod) or iii) “resetting the immune system” by wiping out the existing immune repertoire, including pathogenic myelin reactive clones, then allowing a pool of new and healthy immune cells to Experimental Neurology xxx (2010) xxx–xxx ⁎ Corresponding author. E-mail address: Jls53@medschl.cam.ac.uk (J.L. Jones). YEXNR-10556; No. of pages: 6; 4C: 0014-4886/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.expneurol.2010.06.003 Contents lists available at ScienceDirect Experimental Neurology journal homepage: www.elsevier.com/locate/yexnr Please cite this article as: Jones, J.L., Coles, A.J., New treatment strategies in multiple sclerosis, Exp. Neurol. (2010), doi:10.1016/j. expneurol.2010.06.003