A Clinical Trial Will Test Exercise for Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease of the brain and spinal cord. In MS, aberrant immune cells mistakenly target and strip myelin away from nerve fibres. Nerve fibres carry information as electrical signals between neurons and between neurons and other cells in the body. A bared nerve fibre carries electrical signals slower and may degenerate if its lost myelin is not replaced. Research suggests the degeneration of nerve fibres is a major determinant of progression and permanent disability in MS.

Oligodendrocytes are cells that generate myelin. Like an octopus extending a tentacle to grab a cable, the oligodendrocyte extends its processes to encircle nearby nerve fibres. When myelin is lost, immature oligodendrocytes can be coaxed to generate new myelin in a process called remyelination. In a 2021 review written for the Journal of Neurology, Drs. Nick Cunniffe and Alasdair Coles state that the greatest unmet need in MS is treatments that delay, prevent, or reverse progression. They then state that remyelination is one of the most tractable strategies to fill this unmet need.

A clinical trial is currently being conducted in Portland, Oregon, that will test if exercise can promote remyelination. The trial is a randomized, single-blind study sponsored by the Oregon Health and Science University and led by Principal Investigator Dr. Lindsey Wooliscroft. With an estimated enrollment of 60 participants, the trial will compare 24 weeks of stationary cycling to MS education (the control group). “There is an urgent need to restore activity and participation in people with MS, and remyelination is the most promising therapeutic strategy to accomplish this goal,” writes Wooliscroft in the clinical trial record detail.

According to UpToDate, a resource written and edited by physicians and used by medical professionals to access the most current clinical evidence, exercise is recommended for people with MS. Exercise is a nonpharmacological intervention for common symptoms of the disease like depression, fatigue, and spasticity. Clinical research also shows increases in mobility, balance, and motor coordination after exercise.

People living with MS can exercise at different stages of the disease and with varying levels of disability. There are specialized adapted fitness centers that provide a space for adults and children with physical disabilities to exercise.

Martin has been living with MS for 22 years. He uses an adapted cycle that allows him to exercise from his wheelchair. The screen attached to the cycle tells him how fast he is going, how much work his legs are doing, and how much the machine is assisting him. Exercise has been part of his routine for the last nine years. “Quite honestly, if I didn’t do this, I think I’d be worse,” he says.

Michelle has been living with MS for ten years and began exercising regularly in 2019. When talking about her progress in the gym, she says it’s a very exciting part of the journey, “I’m getting stronger in small ways. It’s a matter of inches. But when you gain, you gain.”

A pre-clinical animal study suggests exercise can directly increase remyelination. Completed in 2018 by Dr. Samuel Jensen and colleagues in the lab of Dr. V. Wee Yong at the University of Calgary in Canada, mice were given free access to a running wheel after the injection of a toxin into their spinal cord that strips nerve fibres of myelin. Exercise enhanced the rate of remyelination and the proportion of nerve fibres that were remyelinated. In this study, exercise influenced a protein that regulates energy metabolism within oligodendrocytes.

Finding a therapy that promotes remyelination in MS is not an easy task. As Wooliscroft and colleagues state in a 2019 review for Current Treatment Options in Neurology, there are no approved therapies promoting remyelination, and several recent clinical trials of remyelination therapies have shown negative or modest results. “[The trial] results could highlight challenges translating pre-clinical studies into subjects with MS and current strategies to measure remyelination,” write the authors.

Yet researchers remain optimistic. “Simply restoring the myelin sheath, we’re able to both preserve the health of the [nerve fibre] and restore its function,” says Dr. Andrew Caprariello, a senior scientist at a pharmaceutical company who is not involved in the Oregon clinical trial. Modulating immune function in MS reduces clinical relapses (times when disability temporarily worsens), says Caprariello. Yet the disease progresses, nonetheless. “That indicates that there needs to be an additional element that targets the brain. Is that remyelination? I hope so.”