Emerging drugs for primary progressive multiple sclerosis

ABSTRACT

Introduction: The identification of effective therapies for progressive forms of multiple sclerosis (MS) has remains a priority and challenge for the global MS community. Despite a few proposed mechanisms, a more complete understanding of the mechanisms involved in the pathogenesis of these MS phenotypes, animal models that incorporate these pathogenic characteristics, novel trial designs, drug repurposing strategies, and new models of collaboration between clinical and basic science personnel may be required in identifying effective therapies.

Areas covered: Here, we review the current knowledge on putative pathogenic mechanisms in primary progressive MS (PPMS). Also, the rationale and outcomes of key phase II or III trial initiatives in PPMS are summarized. Future perspectives are outlined.

Expert opinion: The recent approval of ocrelizumab is a major milestone forward in the therapy of PPMS. One reason for success of this drug is appropriate patient selection. The ultimate goal in PPMS therapy should be the reversal of disability, and the arrest of disease progression. Our current understanding of PPMS suggests that a combination of immune-modulatory, myelin-restorative, and neuro-regenerative therapies particularly early in the disease course would be a reasonable strategy. Finally, selection of appropriate patients, selection of appropriate outcomes and monitoring therapy is again crucial for success of therapeutic strategies.

KEYWORDS:

• animal models
• experimental autoimmune encephalomyelitis
• EAE
• multiple sclerosis
• MS
• primary-progressive multiple sclerosis
• ocrelizumab
• regeneration
• treatment
• therapy
• clinical trials

Declaration of interest

T Forsthuber received grant support NS084201 from the National Institute of Health (TGF), and RG5501 from the National Multiple Sclerosis Society (TGF).

O Stüve is funded by a Merit Review grant (federal award document number (FAIN) I01BX001674) from the United States (U.S.) Department of Veterans Affairs, Biomedical Laboratory Research and Development. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. A reviewer on this manuscript has disclosed that they have been a consultant for AbbVie, Accordant, Acorda, Bayer, Biogen, Celgene, Genentech/Roche, Novartis, Sanofi Genzyme, Serono and Teva; and received research grants from Actelion, Alkermes, Genentech/Roche, MedDay, NINDS, Novartis and Opexa.

Additional information

Funding

This paper was not funded.