Age-related effects of MS may prove reversible

HSCI scientists and collaborators at the University of Cambridge in the United Kingdom have found that the age-related degeneration in conditions such as multiple sclerosis (MS) may be reversible.

The team, co-led by HSCI Executive Committee member Amy Wagers, PhD, has found that impairment of the body’s ability to replace protective myelin sheaths, which surround nerve fibers and allow them to send signals properly, may be reversible, offering new hope that therapeutic strategies aimed at restoring efficient regeneration can be effective in the central nervous system throughout life.

In a proof-of-principle study published in the journal Cell Stem Cell, the researchers report that defects in the regeneration of the myelin sheaths, which are lost in diseases such as MS, may be at least partially corrected after exposing an old animal to the circulatory system of a young animal. Myelin is a fatty substance that protects nerves and aids in the quick transmission of signals between nerve cells.

Using a surgical technique, the researchers introduced an experimental demyelinating injury in the spinal cord of an old mouse, creating small areas of myelin loss, and then exposed those areas to cells found in the blood of a young mouse. By doing so, they found that the influx of certain immune cells, called macrophages, from the young mouse helped resident stem cells restore effective remyelination in the old mouse’s spinal cord. This rejuvenating effect of young immune cells was aided in part by the greater efficiency of the young cells in clearing away myelin debris created by the demyelinating injury. Prior studies have shown that this debris impedes the regeneration of myelin.

“Aging impairs regenerative potential in the central nervous system,” said Wagers, who co-led the study with Professor Robin Franklin, director of the MS Society’s Cambridge Centre for Myelin Repair at the University of Cambridge. “This impairment can be reversed, however, suggesting that the eventual development of cell-based or drug-based interventions that mimic the rejuvenation signals found in our study could be used therapeutically.”

This could be particularly useful, she said, in treating MS, which typically spans many decades of life, and thus is likely to be influenced by age-dependent reductions in the ability of myelin to regenerate. In MS, the body’s own immune system attacks the myelin sheath and prevents nerve fibers in the brain from sending signals properly, which can cause mild symptoms such as limb numbness or more serious ones like losing the ability to walk or speak. As people with MS age, remyelination decreases significantly, eventually causing permanent loss of nerve fibers.

“For MS sufferers,” said Franklin, “this means that, in theory, regenerative therapies will work throughout the duration of the disease. Specifically, it means that remyelination therapies do not need to be based on stem cell transplantation, since the stem cells already present in the brain and spinal cord can be made to regenerate myelin, regardless of a person’s age.”

The next steps toward achieving the goal of boosting the endogenous repair capacity of precursor cells already present in the nervous system will be to better understand how young inflammatory cells boost remyelinating activity. While it is known that this is linked in part to their ability to clear myelin debris left behind after

demyelinating injury, scientists don’t have a clear picture of what determines that ability or how they might be able to regulate it. It is also clear that additional signals that are unrelated to the influx of these young inflammatory cells also play an important role in determining repair capacity. The team hopes to uncover these signals as well, and to evaluate their therapeutic potential in demyelinating injury.

As deficits in regenerative abilities occur in many tissues throughout the body as a result of advancing age, the researchers will also be extending their findings to other age-affected organs to determine if alterations in the induced inflammatory response may be a common mechanism by which tissue repair is impeded by aging.