Update on immunopathogenesis and immunotherapy in multiple sclerosis

Figures & data

Figure 1 Immunopathogenesis of multiple sclerosis.

Abbreviations: Treg, regulatory T cell; NK cell, natural killer cell; IL, interleukin.

Figure 2 Established and emerging multiple sclerosis therapies.

Abbreviations: IFN-β, interferon beta; GA, glatiramer acetate; BG-12, dimethyl fumarate; FTY, fingolimod; NK cell, natural killer cell.

Table 1 Summary of application, assumed mode of action, and current status of drug development

Drug (brand name)	Administration	(Assumed) mode of action	Status of development
Interferon beta-1a (Avonex^® [Biogen Idec])	Intramuscularly once a week	Effects on cytokines, chemokines, and metalloproteinases, modulation of lymphocyte	Approved (CIS, RRMS)
Interferon beta-1b (Betaferon^®, [Bayer]), Betaseron^®, [Bayer], Extavia^® [Novartis])	Subcutaneously every other day	activation and migration, proliferation of regulatory T cells	Approved (CIS, RRMS; and SPMS with ongoing relapse activity in Europe)
Interferon-beta 1a (Rebif^® [Merck Serono])	Subcutaneously three times a week
Glatiramer acetate (Copaxone^® [Teva])	Subcutaneously once daily	Alteration of the cytokine profile of T cells and monocytes, induction of regulatory T cells, induction of neurotrophic factors in immune cells	Approved (CIS, RRMS)
Mitoxantrone (Ralenova^® [MEDA Pharma])	Intravenously every three months	DNA strand breakage and inhibition of DNA repair	Approved (highly progressive SPMS, third line in highly active RRMS)
Natalizumab (Tysabri^® [Biogen Idec])	Intravenously every 4 weeks	Inhibition of lymphocyte migration across the blood–brain barrier and into the CNS	Approved (highly active or breakthrough RRMS)
Fingolimod (Gilenya^® [Novartis])	Orally once daily	Inhibition of lymphocyte egress from secondary lymphoid tissue	Approved (highly active RRMS in Europe, baseline therapy of RRMS in the US)
Alemtuzumab (Campath 1H^® [Genzyme])	Intravenously	Depletion of lymphocytes, monocytes, eosinophils, thymocytes	Phase III (RRMS) completed
Rituximab (MabThera^® [Hoffmann-La Roche], Rituxan^® [Biogen Idec])	Intravenously	Depletion of CD20+ B lymphocytes	Phase II (RRMS, PPMS)
Ocrelizumab	Intravenously		Phase III (RRMS, PPMS)
Ofatumumab (Arzerra^®, [GlaxoSmithKline], HuMax-CD20^® [GlaxoSmithKline])	Intravenously		Pilot trial (RRMS)
Laquinimod	Orally	Modulation of the Th1/Th2 balance towards a Th2 response	Phase III (RRMS) completed
BG00012 (Tecfidera® [Biogen Idec])	Orally	Inhibition of synthesis of proinflammatory cytokines	Phase III (RRMS) completed/approved in the US (RRMS)
Teriflunomide (Aubagio^® [Sanofi Aventis])	Orally	Inhibition of de novo pyrimidine synthesis in activated lymphocytes	Phase III (RRMS, CIS) completed/approved in the US (RRMS)
Daclizumab (Zenapax^® [Hoffmann-La Roche])	Intravenously	Inhibition of proliferation of several immune cells	Phase III (RRMS)

Abbreviations: RRMS, relapsing-remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis; PPMS, primary progressive multiple sclerosis; CIS, clinically isolated syndrome; CNS, central nervous system; Th, T-helper.