Aerobic Exercise for Remyelination in Multiple Sclerosis

Multiple sclerosis (MS) is the most common non-traumatic disabling neurologic condition of young adulthood, affecting more than 2.5 million people worldwide. Permanent disability in MS is caused by recurrent demyelination due to episodic inflammation, followed by neuronal damage, axonal degeneration, and progressive failure of remyelination. There is an urgent need to restore activity and participation in people with MS (pwMS), and remyelination is the most promising therapeutic strategy to accomplish this goal.

Remyelination in pwMS will likely require integration of pharmacologic and rehabilitative approaches to ensure effective remyelination of appropriate neural pathways. Aerobic exercise is an ideal complement to remyelinating medications because aerobic exercise 1) improves walking function in pwMS, and 2) promotes remyelination in animal models both independently and synergistically with medications. However, there are many unknowns that need to be addressed before aerobic exercise can be explored in multimodal clinical trials for remyelination. First, it is imperative to understand how myelination impacts disability in MS, as many other factors could contribute to reduced activity and participation. Additionally, as remyelination occurs over 12 to 24 weeks, it is imperative to establish the feasibility of similar duration of aerobic exercise interventions, and explore if exercise independently influences established remyelination outcomes before integration into multimodal strategies.

This is a randomized, single-blind, parallel clinical trial of a 24-week aerobic stationary cycling intervention to determine feasibility and explore if aerobic exercise independently promotes remyelination in pwMS.

Inclusion criteria

• Physician-confirmed diagnosis of MS based on the 2017 McDonald criteria
• 18-64 years old
• Have access to the internet and a device that can access virtual visits
• (Inclusion criteria to advance to clinical trial) Somatosensory evoked potential (SSEP) latency z-score ≥2 for P40 or inter-side difference in z-score ≥2 for P40

Exclusion criteria

• Medical or biophysical conditions that prohibit the use of a cycle ergometer or treadmill (medical readiness to be assessed by the Activity Readiness Questionnaire (PAR-Q)) or achievement of target heart rate.
• Engages in >30 minutes/week of aerobic activity regularly.
• Clinically confirmed MS relapse in the last 3 months.
• Changes in disease modifying therapy (DMT) for MS in the last 6 months.
• Pregnant women.
• Treatment with steroids for MS in the last 30 days.
• Concurrent use of 4-aminopyridine or dalfampridine (medications which can alter SSEP) and unwilling to discontinue it for 2 days prior to SSEP testing.
• Have a known history of severe spinal canal stenosis