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Published on: September 12, 2016
Emerging therapies to target CNS pathophysiology in multiple sclerosis
Jiwon Oh1,2, Amit Bar-Or3
1Division of Neurology, Department of Medicine, St. Michael's Hospital, University of Toronto, Ontario, Canada.
Abstract:
The rapidly evolving therapeutic landscape of multiple sclerosis (MS) has contributed to paradigm shifts in our understanding of the biological mechanisms that contribute to CNS injury and in treatment philosophies. Opportunities remain to further improve treatment of relapsing-remitting MS, but two major therapeutic gaps are the limiting of progressive disease mechanisms and the repair of CNS injury. In this Review, we provide an overview of selected emerging therapies that predominantly target processes within the CNS that are thought to be involved in limiting non-relapsing, progressive disease injury or promoting tissue repair. Among these, we consider agents that modulate adaptive and innate CNS-compartmentalized inflammation, which can be mediated by infiltrating immune cells and/or resident CNS cells, including microglia and astrocytes. We also discuss agents that target degenerative disease mechanisms, agents that might confer neuroprotection, and agents that create a more favourable environment for or actively contribute to oligodendrocyte precursor cell differentiation, remyelination and axonal regeneration. We focus on agents that are novel for MS, that are known to or are presumed to penetrate the CNS, and that have already entered early stages of development in MS clinical trials.
Insights
Emerging therapies for multiple sclerosis (MS) aim to address progressive disease and CNS injury by targeting inflammation, neurodegeneration, and promoting repair mechanisms like remyelination and axonal regeneration.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- The therapeutic landscape for multiple sclerosis (MS) is rapidly evolving, necessitating new treatment strategies.
- Current treatments for relapsing-remitting MS have limitations, with significant unmet needs in addressing progressive disease mechanisms and repairing central nervous system (CNS) injury.
Purpose of the Study:
- To review emerging therapies for MS that target CNS-specific processes.
- To highlight agents aimed at limiting progressive disease injury and promoting tissue repair in the CNS.
Main Methods:
- Focus on novel agents for MS that are known or presumed to penetrate the CNS.
- Review therapies targeting inflammation, neurodegeneration, neuroprotection, and remyelination/axonal regeneration.
- Consider agents in early-stage clinical development for MS.
Main Results:
- Emerging therapies modulate adaptive and innate CNS-compartmentalized inflammation involving immune cells, microglia, and astrocytes.
- Agents targeting degenerative mechanisms, conferring neuroprotection, and promoting oligodendrocyte precursor cell differentiation, remyelination, and axonal regeneration are discussed.
- The review focuses on therapies with potential to address key therapeutic gaps in MS management.
Conclusions:
- Novel therapeutic strategies are under investigation to address progressive multiple sclerosis and CNS repair.
- These emerging agents target diverse mechanisms including inflammation, neuroprotection, and regeneration.
- Further clinical development is crucial to evaluate the efficacy of these promising therapies for MS patients.
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