Therapeutic Advances and Future Prospects in Progressive Forms of Multiple Sclerosis

Abstract

Identifying effective therapies for the treatment of progressive forms of multiple sclerosis (MS) is a highly relevant priority and one of the greatest challenges for the global MS community. Better understanding of the mechanisms involved in progression of the disease, novel trial designs, drug repurposing strategies, and new models of collaboration may assist in identifying effective therapies. In this review, we discuss various therapies under study in phase II or III trials, including antioxidants (idebenone); tyrosine kinase inhibitors ( m a s i t i n i b ) ; s p h i n g o s i n e r e c e p t o r m o d u l a t o r s (siponimod); monoclonal antibodies (anti-leucine-rich repeat and immunoglobulin-like domain containing neurite outgrowth inhibitor receptor-interacting protein-1, natalizumab, ocrelizumab, intrathecal rituximab); hematopoetic stem cell therapy; statins and other possible neuroprotective agents (amiloride, riluzole, fluoxetine, oxcarbazepine); lithium; phosphodiesterase inhibitors (ibudilast); hormone-based therapies (adrenocorticotrophic hormone and erythropoietin); T-cell receptor peptide vaccine (NeuroVax); autologous T-cell immunotherapy (Tcelna); MIS416 (a microparticulate immune response modifier); dopamine antagonists (domperidone); and nutritional supplements, including lipoic acid, biotin, and sunphenon epigallocatechin-3-gallate (green tea extract). Given ongoing and planned clinical trial initiatives, and the largest ever focus of the global research community on progressive MS, future prospects for developing targeted therapeutics aimed at reducing disability in progressive forms of MS appear promising.

The link of inflammation and neurodegeneration in progressive multiple sclerosis

“…However, the lack of biomarkers predicting the level of activity and/or progression in MS, namely active demyelination and neurodegeneration, hinders the stratification of disease types [11,18]. In this regard, further promising developments in PMS therapies with targeted disease-modifying drugs may contribute to better understanding the underlying molecular and cellular pathology of MS. Lastly, but not least, global research collaboration will be needed to overcome the challenges of understanding and treating efficiently PMS [23,58].…”

The future of multiple sclerosis treatments

“…The current treatment candidates and approaches for progressive MS have been recently reviewed in detail by Shirani et al [105]. An important point in testing drugs for progressive forms of MS is to adapt trial methodology and clinically meaningful outcomes to this particular phenotype of MS, based on lessons learned from prior clinical trials [106].…”

Nogo-A Antibodies for Progressive Multiple Sclerosis

“…However, many lessons were learned from preclinical [18] and clinical trials [16]. Additionally, promising new drug candidates are currently in development (reviewed in [19]). …”