Abstract
The treatment of multiple sclerosis (MS) has changed over the last 20 years. All immunotherapeutic drugs target relapsing remitting MS (RRMS) and it still remains a medical challenge in MS to develop a treatment for progressive forms. The most common injectable disease-modifying therapies in RRMS include β-interferons 1a or 1b and glatiramer acetate. However, one of the major challenges of injectable disease-modifying therapies has been poor treatment adherence with approximately 50% of patients discontinuing the therapy within the first year. Herein, we go back to the basics to understand the immunopathophysiology of MS to gain insights in the development of new improved drug treatments. We present current disease-modifying therapies (interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, mitoxantrone), humanized monoclonal antibodies (natalizumab, ofatumumab, ocrelizumab, alemtuzumab, daclizumab) and emerging immune modulating approaches (stem cells, DNA vaccines, nanoparticles, altered peptide ligands) for the treatment of MS.
Highlights
In the early 1900s, only a few cases of multiple sclerosis (MS) were reported, which quickly became a common occurrence for admission to neurological wards
Altered peptide ligands (APL) are peptides closely related to the native peptide with defined 1–2 substituted amino acid residues which interact with the T cell receptor (TCR) yet retains its binding ability to the MHC [65]
MS is an autoimmune disorder of the central nervous system (CNS) with an array of immune cells being either activated or suppressed leading to demyelination and disease progression
Summary
In the early 1900s, only a few cases of multiple sclerosis (MS) were reported, which quickly became a common occurrence for admission to neurological wards. MS symptoms and disease progression are varied, with some individuals experiencing little disability while most (up to 60%) require a wheelchair 20 years from diagnosis [9]. MS lesions may form in any location of the CNS white matter or in grey matter, often leading to physical disability and sometimes, decline in cognitive ability [16,18]. It is conceivable to target immune cells and their products in order to prevent tissue damage by modulating inflammation [9,19] while reducing potential side effects such as global immunosuppression [6,19,20]. The major constituents of the myelin sheath in which autoreactive T cells and antibodies recognize, include, myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG) and proteolipid protein (PLP)
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