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Primary progressive multiple sclerosis: current therapeutic strategies and future perspectives
Alberto Gajofatto1, Marco Turatti2, Maria Donata Benedetti2
1a Department of Neuroscience, Biomedicine and Movement Sciences , University of Verona , Verona , Italy.
Introduction:
Multiple sclerosis (MS) is a chronic inflammatory condition of the central nervous system with heterogeneous features. Primary progressive (PP) MS is a rare disease subtype characterized by continuous disability worsening from onset. No disease-modifying therapy is currently approved for PP MS due to the negative or inconsistent results of clinical trials conducted on a wide range of interventions, which are reviewed in the present paper. Areas covered: The features and results of randomized trials of disease-modifying treatments for PP MS are discussed, including immunosuppressants, immunomodulators, monoclonal antibodies, and putative neuroprotective agents. Expert commentary: The recent encouraging results of the ocrelizumab trial in PP MS, the first to reach the primary disability endpoint, indicate B cells as a promising therapeutic target to prevent disease progression. Other emerging treatment strategies include cell metabolism modulation and inflammatory pathways inhibition, which are being investigated in several ongoing phase II and III placebo-controlled trials. Future PP MS trials will need to systematically include efficacy endpoints other than physical disability alone, such as cognition, quality of life, advanced MRI measures and molecular biomarkers.
Insights
No approved treatments exist for primary progressive multiple sclerosis (PP MS). Ocrelizumab shows promise by targeting B cells, offering hope for future therapies and improved outcomes.
Area of Science:
- Neuroimmunology
- Clinical Neurology
- Pharmacology
Background:
- Multiple sclerosis (MS) is a chronic, heterogeneous central nervous system inflammatory disease.
- Primary progressive multiple sclerosis (PP MS) is a rare subtype with continuous worsening disability.
- Current disease-modifying therapies lack approval for PP MS due to trial inconsistencies.
Purpose of the Study:
- To review randomized trials of disease-modifying treatments for PP MS.
- To discuss the efficacy of various interventions, including immunosuppressants, immunomodulators, and monoclonal antibodies.
- To highlight emerging therapeutic strategies and future trial considerations.
Main Methods:
- Systematic review of randomized clinical trials for PP MS treatments.
- Analysis of trial results for immunosuppressants, immunomodulators, monoclonal antibodies, and neuroprotective agents.
- Evaluation of the ocrelizumab trial and its implications.
Main Results:
- The ocrelizumab trial is the first to meet a primary disability endpoint in PP MS.
- B cell targeting demonstrates potential for preventing disease progression.
- Ongoing trials investigate cell metabolism modulation and inflammatory pathway inhibition.
Conclusions:
- B cells represent a promising therapeutic target for PP MS.
- Future PP MS trials should incorporate broader efficacy endpoints beyond physical disability.
- Cognition, quality of life, advanced MRI, and biomarkers are crucial for future assessments.
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