An exercise hormone may ease MS symptoms by protecting nerve cells from damage, early research in mice suggests.
Irisin, a hormone released during exercise, appeared to directly shield neurons from damage in a mouse model of multiple sclerosis.
An experimental gene therapy raised blood levels of the hormone, reducing clinical disability and limiting nerve cell loss in the spinal cord, hippocampus and retina of the mice.
Irisin’s protective effects appeared to work independently of the immune system, pointing to a possible new strategy for MS drug development.
When researchers deleted the gene that makes irisin, the protective effects of exercise disappeared.
Sina Rosenkranz, first author and head of the Behavioral Interventions group at the Institute for Neuroimmunology and Multiple Sclerosis at UKE, said: “What we find particularly exciting is that [the work reveals] a fundamentally new mechanism by which exercise can influence neurodegeneration in MS.”
The researchers said irisin appears to act directly on neurons rather than by suppressing the immune system.
Multiple sclerosis is a long-term autoimmune condition in which the immune system attacks myelin, the protective coating around nerves in the brain and spinal cord.
This damage can disrupt messages between the brain and body, causing progressive neurological disability.
Current MS treatments can reduce inflammation, but the researchers said approved therapies do not directly target nerve cells to stop their loss.
Research has shown that aerobic exercise can improve MS symptoms, but the exact biological mechanisms have remained unclear.
Wrann and colleagues have previously shown that irisin can improve cognitive function and reduce neuroinflammation in mouse models of Alzheimer’s disease.
The new study found similar neuroprotective effects in the mouse model of MS.
Mice that exercised on running wheels before developing MS and during the disease showed less nerve cell loss and milder symptoms than sedentary animals.
These benefits disappeared in mice with the gene encoding irisin deleted.
In further experiments, deleting irisin again cancelled out the protective effects of exercise, while delivering irisin through gene therapy rescued neurons and improved disease outcomes.
Gene therapy is an approach that uses genetic instructions to change how cells behave or make specific proteins.
Irisin reduced nerve cell loss in three parts of the animals’ central nervous system: the spinal cord, hippocampus and retina.
The hippocampus is a brain region involved in memory, while the retina is the light-sensitive tissue at the back of the eye.
Irisin also reduced synapse loss and restored a protective gene programme in spinal cord neurons.
Synapses are the connections that allow nerve cells to communicate.
The researchers said irisin appeared to act directly on neurons rather than by dampening the immune response.
No significant differences in immune cell activity were seen between irisin-treated and control animals.
The researchers said this pathway complements earlier work showing that some benefits of exercise come from changes in the immune system, suggesting several biological mechanisms may contribute to exercise’s protective effects in the brain.
Ruxandra Sîrbulescu, co-senior author and assistant professor of neurology at Harvard Medical School, said: “Interestingly, in the current study we did not find a direct suppressive effect of irisin on peripheral immunity, but rather direct neuroprotective effects.”
The authors said more research is needed to understand exactly how irisin protects neurons.
They also said exercise is likely to affect MS through several biological pathways, meaning irisin alone may not explain all of its benefits.
Further work will be needed to determine whether the findings translate to people living with MS.
