Primary progressive multiple sclerosis: current therapeutic strategies and future perspectives.
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.
a Department of Neuroscience, Biomedicine and Movement Sciences , University of Verona , Verona , Italy.
Alberto
A
Gajofatto
b Department of Neuroscience , Azienda Ospedaliera Universitaria Integrata Verona , Verona , Italy.
Marco
M
Turatti
b Department of Neuroscience , Azienda Ospedaliera Universitaria Integrata Verona , Verona , Italy.
Maria Donata
MD
Benedetti
D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D011788:Quality of Life
D007155:Immunologic Factors; D007166:Immunosuppressive Agents
Multiple sclerosis; disease-modifying therapy; immunomodulatory drugs; immunosuppressive drugs; ocrelizumab; primary progressive; treatment