Progressive multiple sclerosis: Evaluating current therapies and exploring future treatment strategies

Area of Science:

• Neuroimmunology
• Neurology
• Clinical Therapeutics

Background:

• Progressive multiple sclerosis (MS), encompassing primary progressive MS (PPMS) and secondary progressive MS (SPMS), is characterized by continuous neurological decline.
• Unlike relapsing-remitting MS (RRMS), progressive MS features relentless disability accumulation with minimal relapses or new MRI activity.
• Key pathological features include persistent central nervous system (CNS) inflammation, mitochondrial dysfunction, and aberrant immune responses.

Purpose of the Study:

• To review the current management strategies for progressive forms of MS.
• To explore emerging therapeutic avenues targeting the unique pathophysiology of PPMS and SPMS.
• To highlight the unmet need for novel treatments addressing both inflammation and neurodegeneration in progressive MS.

Main Methods:

• Review of current literature on progressive MS pathophysiology and treatment.
• Analysis of the limitations of existing disease-modifying agents (DMAs) in progressive MS.
• Exploration of potential future therapeutic targets and approaches.

Main Results:

• Neurological worsening in MS is primarily driven by the progressive disease course, leading to accumulating disability.
• Existing DMAs have shown limited efficacy in managing progressive MS compared to RRMS.
• The pathophysiology involves CNS-specific inflammation, mitochondrial issues, and immune system alterations.

Conclusions:

• Effective management of progressive MS requires addressing its distinct pathological mechanisms, including CNS inflammation and neurodegeneration.
• Novel therapeutic strategies are crucial to overcome the limitations of current treatments in PPMS and SPMS.
• Future research should focus on developing targeted therapies for the complex pathophysiology of progressive MS.