Recent Advances in Interventions Targeting Remyelination and a Systematic Review of Remyelinating Effects of Approved...

Area of Science:

• Neuroscience
• Immunology
• Regenerative Medicine

Background:

• Progressive multiple sclerosis (MS) presents a significant unmet need for regenerative therapies.
• Combining immunomodulatory and remyelinating treatments is a promising therapeutic frontier for MS.
• Identifying disease-modifying treatments (DMT) with pro-remyelinating properties is crucial for future combination therapies.

Purpose of the Study:

• To systematically review preclinical and clinical research on remyelination in MS.
• To evaluate the effects of currently FDA and EMA-approved DMT on remyelination.
• To identify promising DMT for future combination treatments targeting MS pathogenesis.

Main Methods:

• Systematic literature search conducted according to the "Synthesis without meta-analysis" (SWiM) reporting guideline.
• Protocol registered at PROSPERO prior to the search.
• Inclusion of preclinical studies, randomized controlled trials (RCTs), non-randomized clinical studies, and reviews on remyelination in MS.

Main Results:

• Preclinical studies suggest neuroprotective effects for various DMT.
• Convincing evidence of true remyelination in vitro or in vivo was found for glatiramer acetate, teriflunomide, Fingolimod, Siponimod, Ponesimod, and alemtuzumab.
• Clinical trials showed promising results for glatiramer acetate, Fingolimod, Siponimod, natalizumab, alemtuzumab, and ocrelizumab using surrogate markers, but proof of remyelination alone is insufficient.

Conclusions:

• Future MS clinical trials for remyelinating agents should utilize composite endpoints combining multiple outcome measures.
• Development of novel biomarkers is essential to accurately assess repair mechanisms in MS.
• Further research is needed to validate the remyelinating capacity of DMT and their role in MS treatment.