Detecting neurodegenerative pathology in multiple sclerosis before irreversible brain tissue loss sets in

Table 1 Development timeline for disease-modifying therapy in MS

FDA or EMA approval^	Product	Main immunological mechanism of action
1993/1996	INF β-1b/-1a	Induces changes in cytokine balance
1996	Glatiramere acetate	Interferes with antigen presentation to T-lymphocytes
2000	Mitoxantrone	Reduces the number of circulating leukocytes
2004	Natalizumab	Blocks leukocyte migration across the BBB
2010	Fingolimod	Prevents lymphocyte egression from the lymph nodes
2012	Teriflunomide	Inhibits lymphocyte proliferation
2013	Dimethyl fumarate	Induces changes in cytokine balance
2014	Alemtuzumab Pegylated INF β-1a	Destructs circulating lymphocytes, followed by repopulation Induces changes in cytokine balance
2016°	Daclizumab	Induces immune tolerance
2017	Cladribine* Ocrelizumab	Reduces the number of circulating lymphocytes Depletes B-lymphocyte population
2019	Siponimod	Prevents lymphocyte egression from the lymph nodes
Pipeline	Ozanimod and ponesimod Ofatumumab Evobrutinib AHSCT	Prevents lymphocyte egression from the lymph nodes Depletes circulating B-lymphocytes Inhibits B-lymphocyte signaling and maturation Immune system reconstitution

FDA Food and Drug Administration, EMA European Medical Agency, INF interferon, BBB blood-brain barrier, AHSCT autologous stem cell transplantation, MS multiple sclerosis.
^ based on which approval came first
* No FDA approval at present
° Withdrawn in 2018

ISSN: 2047-9158