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Towards Treating Multiple Sclerosis Progression
Darius Häusler1,2, Martin S Weber1,2,3
1Institute of Neuropathology, University Medical Centre, 37075 Goettingen, Germany.
Abstract:
Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS). In most patients, the disease starts with an acute onset followed by a remission phase, subsequent relapses and a later transition to steady chronic progression. In a minority of patients, this progressive phase develops from the beginning. MS relapses are characterized predominantly by the de novo formation of an inflammatory CNS lesion and the infiltration of immune cells, whereas the pathological features of MS progression include slowly expanding lesions, global brain atrophy and an inflammatory response predominantly mediated by macrophages/microglia. Importantly, this CNS-intrinsic pathophysiology appears to initiate early during the relapsing-remitting disease phase, while it turns into the key clinical MS feature in later stages. Currently approved disease-modifying treatments for MS are effective in modulating peripheral immunity by dampening immune cell activity or preventing the migration of immune cells into the CNS, resulting in the prevention of relapses; however, they show limited success in halting MS progression. In this manuscript, we first describe the pathological mechanisms of MS and summarize the approved therapeutics for MS progression. We also review the treatment options for progressive MS (PMS) that are currently under investigation. Finally, we discuss potential targets for novel treatment strategies in PMS.
Insights
Multiple sclerosis (MS) involves central nervous system inflammation and demyelination. Current treatments manage relapses but are less effective for progressive MS (PMS), highlighting the need for new therapeutic strategies.
Area of Science:
- Neuroimmunology
- Neurology
- Pathophysiology
Background:
- Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS).
- MS pathology involves distinct mechanisms during relapsing-remitting and progressive phases, including CNS-intrinsic processes.
- Existing disease-modifying therapies primarily target peripheral immunity and are more effective against relapses than progression.
Purpose of the Study:
- To review the pathological mechanisms underlying MS progression.
- To summarize current therapeutic strategies for progressive MS (PMS).
- To discuss emerging treatment targets for novel PMS therapies.
Main Methods:
- Review of pathological mechanisms in MS progression.
- Summary of approved and investigational therapeutics for PMS.
- Discussion of potential future treatment targets.
Main Results:
- MS progression involves CNS-intrinsic pathophysiology, including slowly expanding lesions and brain atrophy, which initiates early in the disease.
- Current MS treatments effectively reduce relapses but show limited efficacy in halting disease progression.
- Several novel treatment options for PMS are under investigation, targeting different pathological pathways.
Conclusions:
- Understanding the CNS-intrinsic mechanisms of MS progression is crucial for developing effective treatments.
- There is a significant unmet need for therapies that can halt or reverse progressive MS.
- Future research should focus on novel therapeutic targets addressing the specific pathologies of PMS.
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