Bioavailable central nervous system disease-modifying therapies for multiple sclerosis

Area of Science:

• Neuroimmunology
• Pharmacology

Background:

• Multiple sclerosis (MS) therapies often target peripheral immune cells, showing limited efficacy in progressive forms where central nervous system (CNS) pathology is key.
• Current disease-modifying therapies (DMTs) for relapsing MS are primarily studied for peripheral effects, with insufficient evidence for direct CNS impact.

Purpose of the Study:

• To evaluate the potential of existing and novel DMTs to exert direct beneficial effects within the CNS in multiple sclerosis.
• To identify MS therapies that penetrate the blood-brain barrier and may modulate CNS-resident immune cells.

Main Methods:

• Review of existing literature on the pharmacokinetic and pharmacodynamic properties of various MS DMTs.
• Analysis of studies investigating the ability of DMTs to cross the blood-brain barrier and interact with CNS-resident immune cells.

Main Results:

• Most approved MS DMTs (alemtuzumab, fumarates, glatiramer acetates, interferons, mitoxantrone, natalizumab, ocrelizumab, ofatumumab, teriflunomide) are limited to peripheral action or lack confirmed direct CNS effects.
• Cladribine and sphingosine 1-phosphate (S1P) receptor modulators (fingolimod, ozanimod, ponesimod, siponimod) are CNS-penetrant and possess potential for direct CNS-mediated therapeutic benefits.

Conclusions:

• Therapies like cladribine and S1P receptor modulators represent a promising class of MS treatments due to their ability to directly impact the CNS.
• Further research is warranted to fully elucidate the direct CNS effects of these therapies and optimize their use in progressive MS.