Remyelination and neuroprotection translational trials: Lessons from optic neuritis

Area of Science:

• Neuroscience
• Clinical Neurology
• Ophthalmology

Background:

• Multiple sclerosis (MS) treatments reduce inflammation but fail to halt progressive neurodegeneration.
• Remyelination and neuroprotection are critical therapeutic targets for MS.
• The visual pathway, particularly optic neuritis, serves as a valuable model for MS research due to accessible outcome measures.

Purpose of the Study:

• To review preclinical and clinical evidence for remyelinating and neuroprotective agents in optic neuritis.
• To identify key challenges and methodological lessons from past clinical trials.
• To provide insights for improving future translational success in MS therapeutics.

Main Methods:

• Systematic review of preclinical studies and clinical trials (Phase 1-3) evaluating remyelinating and neuroprotective agents in optic neuritis.
• Analysis of visual evoked potentials (VEPs) and optical coherence tomography (OCT) data.
• Synthesis of methodological approaches and outcome measures used in clinical trials.

Main Results:

• Numerous clinical trials have investigated remyelinating and neuroprotective strategies in optic neuritis over two decades.
• No Phase 3 clinical trial has yet met its primary endpoint for remyelination or neuroprotection in this model.
• Identified challenges include optimal intervention timing, patient heterogeneity, assessment variability, and surrogate marker efficacy.

Conclusions:

• Despite extensive research, effective remyelinating and neuroprotective therapies for MS via the optic neuritis model remain elusive.
• Refining clinical trial design, standardizing outcome measures, and exploring combination therapies are crucial for advancing MS treatment.
• Addressing limitations in current trial methodologies is essential for future translational success in combating MS neurodegeneration.