March 27, 2017

Myelin formation, limb function restored in MS mouse models

Multiple sclerosis is a condition whereby the immune system attacks and destroys myelin – the protective coating of nerve fibers – which triggers movement problems characteristic of the disease. Now, researchers say that they may have found a way to restore myelin formation, bringing closer the possibility of new treatments for multiple sclerosis.
The red areas represent where myelin formation was restored in the spinal cord of an MS mouse model after treatment with miR-219.
Image credit: Cincinnati Children’s

In a new study, researchers reveal how a microRNA – called miR-219 – reactivated myelin-producing cells in mouse models of multiple sclerosis (MS), which restored their limb function.

Lead investigator Richard Lu, Ph.D., of the Brain Tumor Center at Cincinnati Children’s Hospital in Ohio, and colleagues recently reported their findings in the journal Developmental Cell.

According to the National Multiple Sclerosis Society, it is estimated that around 2.3 million people worldwide are living with MS.

In MS, the immune system attacks myelin – the fatty substance that protects nerve fibers in the central nervous system (CNS) – as well as the cells that produce myelin, called oligodendrocytes. This causes damage to the nerve fibers, which prevents them from transmitting signals between the brain and spinal cord.

Neurological symptoms arise as a result. These include numbness or tingling in the face, body, or extremities, muscle weakness, and walking difficulties.

With a view to restoring myelin in patients with MS, researchers have increasingly investigated ways to stimulate oligodendrocyte function. In the new study, Lu and colleagues reveal how the microRNA miR-219 could do just that.

Myelin-producing oligodendrocytes activated with miR-219

MicroRNAs are fragments of RNA situated on cell chromosomes that help to regulate gene expression. In some instances, microRNAs inhibit the activity of genes within cells.

Fast facts about MS

  • Women are around two to three times more likely to develop MS than men.
  • Diagnosis of MS most commonly occurs between the ages of 20 and 50.
  • An estimated 8,000 to 10,000 children across the globe are living with MS.

Learn more about MS

Previous studies have shown that the damaged nerves and tissues of patients with MS and other neurodegenerative disease are lacking in miR-219.

With this in mind, Lu and team speculated that miR-219 might have the potential to protect against nerve damage.

For their study, the researchers deleted miR-219 in mouse models of MS and analyzed the effects. The mice had MS-like myelin damage triggered by the autoimmune disorder encephalomyelitis and exposure to the chemical compound lysolecithin.

The researchers found that the absence of miR-219 activated several proteins involved in preventing myelin formation, including a protein called Lingo1.

On further investigation, the team found that miR-219 forms part of a network that inhibits the myelin-producing function of oligodendrocytes.

Next, Lu and colleagues set out to determine whether miR-219 might stimulate oligodendrocyte activity. They did so by using a synthetic version of miR-219 and administering it to the MS mouse models.

The researchers found that miR-219 not only led to myelin regeneration in the mouse models by reactivating oligodendrocyte function, but it also improved the rodents’ limb function.

Based on these findings, Lu and colleagues believe that they may have uncovered a potential new treatment for patients with MS.

“We show that miR-219 targets multiple processes that inhibit myelin formation after nerve injury by the disease process, and that treatment with this microRNA partially restores myelination and limb function.

It is conceivable that augmenting miR-219 treatment with other blockers of myelin regrowth may provide a multipoint treatment strategy for people with demyelinating diseases like MS.”

Richard Lu, Ph.D.

The researchers caution that their study was conducted in mouse models of MS, so their findings cannot yet be applied to humans. The team is now in the process of creating more compounds that simulate miR-219 and that can be more easily administered to humans.

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