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Related Concept Videos

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Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is...
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Measuring Progressive Neurological Disability in a Mouse Model of Multiple Sclerosis
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Progressive multiple sclerosis.

Daniel Ontaneda1, Robert J Fox

  • 1Mellen Center for Multiple Sclerosis, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, USA.

Current Opinion in Neurology
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Summary
This summary is machine-generated.

Progressive multiple sclerosis (PMS) presents neurodegenerative challenges. While past clinical trials for PMS have yielded disappointing results, new treatments and outcome measures are emerging, offering hope for future disease-modifying therapies.

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Area of Science:

  • Neuroimmunology
  • Neurodegeneration
  • Clinical Trial Design

Background:

  • Multiple sclerosis (MS) is a chronic immune-mediated disease with significant neurodegenerative components in its progressive phase.
  • The classification of progressive multiple sclerosis (PMS) has been refined to distinguish between active/inactive inflammatory disease and the presence/absence of gradual progression.
  • This improved classification aids in conceptualizing PMS and potentially enhances clinical trial recruitment.

Purpose of the Study:

  • To review the pathological and clinical features of progressive multiple sclerosis (PMS).
  • To analyze past clinical trial outcomes and explore ongoing trials and novel therapeutic strategies for PMS.
  • To discuss the inherent challenges in designing clinical trials for PMS.

Main Methods:

  • Review of existing literature on progressive multiple sclerosis (PMS) pathology and clinical aspects.
  • Analysis of data from completed and ongoing clinical trials for PMS.
  • Evaluation of emerging treatment options and outcome measures for PMS.

Main Results:

  • Clinical trials using anti-inflammatory drugs effective in relapsing MS have been unsuccessful in PMS.
  • A Phase II trial of simvastatin demonstrated a 43% reduction in annualized atrophy progression in secondary progressive MS.
  • Ongoing trials are investigating treatments such as ibudilast, siponimod, and ocrelizumab, with concurrent development of outcome measures.

Conclusions:

  • Progressive multiple sclerosis (PMS) poses significant challenges due to poorly understood pathogenesis and lack of validated outcome metrics.
  • Despite disappointing trial results to date, advancements in disease understanding and trial design are paving the way for effective disease-modifying agents.
  • Future research and clinical trials are crucial for developing successful treatments for PMS.