title: 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 (masitinib); sphingosine receptor modulators (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.
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Shirani
authors.affiliation: Department of Neurology and Neurotherapeutics, Clinical Center for Multiple Sclerosis, Multiple Sclerosis and Neuroimmunology Imaging Program, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Darin T
authors.initials: DT
authors.lastname: Okuda
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA. olaf.stuve@utsouthwestern.edu.|Neurology Section, VA North Texas Health Care System, Medical Service, Dallas VA Medical Center, Dallas, TX, 75216, USA. olaf.stuve@utsouthwestern.edu.
authors.forename: Olaf
authors.initials: O
authors.lastname: Stüve
mesh_terms: D002986:Clinical Trials as Topic; D005544:Forecasting; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D007155:Immunologic Factors
keywords: Clinical trials; Multiple sclerosis; Primary progressive; Progression; Secondary progressive; Therapeutics