Immunotherapies in progressive multiple sclerosis.

Area of Science:

• Neuroimmunology
• Neurodegeneration
• Central Nervous System Disorders

Background:

• Multiple sclerosis (MS) is an autoimmune central nervous system disease with genetic and environmental risk factors.
• While relapsing and progressive courses are known, disease progression is now recognized as the primary driver of neurological disability in MS patients.
• Understanding the pathophysiology of MS progression is crucial for developing targeted therapies.

Purpose of the Study:

• To highlight the critical role of disease progression in accumulating neurological disability in multiple sclerosis.
• To emphasize the need to define the dominant pathophysiologic processes driving MS progression.
• To discuss the implications of advancing knowledge for developing targeted immunomodulatory treatments.

Main Methods:

• Review of current understanding of MS pathophysiology, focusing on progressive aspects.
• Analysis of pathological hallmarks including central nervous system inflammation and neurodegeneration.
• Examination of evolving clinical trial designs and assessment measures for MS progression.

Main Results:

• Progressive elements are the dominant factor for neurological disability accumulation across all MS clinical courses.
• Pathologic hallmarks include compartmentalized central nervous system inflammation and neurodegenerative processes, leading to neuroaxonal and synaptic loss.
• Growing understanding of pathophysiology supports the development of targeted immunomodulatory treatments for progressive MS.

Conclusions:

• Defining the dominant pathophysiologic processes driving MS progression is indispensable.
• Novel clinical trial designs and advanced assessment measures offer opportunities for personalized treatment regimens.
• Targeted immunomodulatory treatments are emerging for progressive MS based on improved pathophysiologic understanding.