Emerging small-molecule treatments for multiple sclerosis: focus on B cells [version 1; peer review: 2 approved]

• Published in: F1000 research Vol. 8; p. 245
• Main Authors: Gregson, Aaron, Thompson, Kaitlyn, Tsirka, Stella E, Selwood, David L
• Format: Journal Article
• Language: English
• Published: England Faculty of 1000 Ltd 2019; F1000 Research Limited; F1000 Research Ltd
• Subjects: Animals; Antigens; Antineoplastic Agents; Antiviral agents; B-Lymphocytes - physiology; Brain research; Cell death; Cytotoxicity; Drug development; Gene expression; Genomes; Immune system; Immunoglobulins; Immunosuppressive agents; Infections; Inflammation; Lymphocytes B; Mice; Mononucleosis; Multiple sclerosis; Multiple Sclerosis - immunology; Multiple Sclerosis - therapy; Myelin; NMR; Nuclear magnetic resonance; Pathology; Review; Small Molecule Libraries; Vitamin D; Multiple sclerosis; sustainable healthcare; B cells; MS; small molecule drugs
• ISSN: 2046-1402; 2046-1402
• DOI: 10.12688/f1000research.16495.1

Multiple sclerosis (MS) is a major cause of disability in young adults. Following an unknown trigger (or triggers), the immune system attacks the myelin sheath surrounding axons, leading to progressive nerve cell death. Antibodies and small-molecule drugs directed against B cells have demonstrated good efficacy in slowing progression of the disease. This review focusses on small-molecule drugs that can affect B-cell biology and may have utility in disease management. The risk genes for MS are examined from the drug target perspective. Existing small-molecule therapies for MS with B-cell actions together with new drugs in development are described. The potential for experimental molecules with B-cell effects is also considered. Small molecules can have diverse actions on B cells and be cytotoxic, anti-inflammatory and anti-viral. The current B cell-directed therapies often kill B-cell subsets, which can be effective but lead to side effects and toxicity. A deeper understanding of B-cell biology and the effect on MS disease should lead to new drugs with better selectivity, efficacy, and an improved safety profile. Small-molecule drugs, once the patent term has expired, provide a uniquely sustainable form of healthcare.