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Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination

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It's Time For Combination Therapies: in Multiple Sclerosis.

Jagannadha Avasarala¹

¹Dr. Avasarala is Associate Professor of Neurology, Division of Neurology, Department of Medicine, University of South Carolina School of Medicine, Greenville Health System, Greenville, South Carolina.

Innovations in Clinical Neuroscience

|October 6, 2017

Summary

B-cell therapies for multiple sclerosis (MS) show promise but are limited by the blood-brain barrier. Future MS treatments may combine these therapies with agents that can cross this barrier to target brain-specific disease progression.

Keywords:

Blood-brain barrier combination therapies cyclophosphamide disability status drug development laquinimod monoclonal antibodies multiple sclerosis siponimod

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Area of Science:

Neurology
Immunology
Pharmacology

Background:

Multiple sclerosis (MS) treatment is advancing, yet disability progression persists despite B-cell depleting therapies.
Current B-cell therapies for MS cannot penetrate the blood-brain barrier (BBB), limiting their efficacy against central nervous system (CNS) pathology.

Discussion:

The BBB represents a significant obstacle for effective MS treatment, preventing peripherally administered drugs from reaching CNS targets.
B-cells play a critical role in MS pathogenesis, and their migration into the brain exacerbates disease progression and treatment resistance.

Key Insights:

B-cell depleting monoclonal antibodies are a key therapeutic class in MS, but their inability to cross the BBB is a major limitation.
Understanding the pathophysiological role of B-cells within the brain is crucial for developing more effective MS therapies.

Outlook:

Future MS drug development should focus on strategies that overcome the BBB.
Combining peripherally acting B-cell depleting agents with BBB-penetrating molecules offers a promising avenue for future MS therapeutics.