Multiple sclerosis (MS) is a progressive neurological disease that occurs when the immune system attacks myelin, the protective sheath around nerves. Researchers at Cincinnati Children's Hospital Medical Center are investigating a way to restore that shield, using short segments of RNA known as microRNAs.
One particular microRNA called miR-219 seems to stimulate the rebuilding of myelin, the scientists reported in the journal Developmental Cell. They tested their theory by injecting miR-219 into the spines and cerebral spinal fluid of mice that are used as models of MS. They observed that the treatment restored the function of cells called oligodendrocytes, which normally produce myelin, according to a press release.
"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," said lead author Q. Richard Lu, Ph.D., director of the Brain Tumor Center at Cincinnati Children's, in the release.
MicroRNAs, which reside on the chromosomes of cells, act to regulate gene expression in a way that maintains the body’s normal functioning. The absence of miR-219 had previously been noted in MS and other neurodegenerative disorders. While investigating the activity of the microRNA in mouse models of MS, Lu and his team observed that its absence stimulated certain proteins that block the formation of myelin. So they synthesized miR-219 and tried it as a treatment to restore myelination.
Many efforts are underway to protect and restore myelin in MS. Investigators at the University of Chicago, for example, have been looking at the potential of an FDA-approved blood pressure drug called Wytensin (guanabenz) to prevent the loss of myelin. And Acorda is in phase 1 trials of rHIgM22, a molecule licensed from the Mayo Clinic that’s designed to remyelinate nerve cells. Biogen has been investigating a drug that acts against Lingo—one of the proteins that inhibits myelin formation—but results have been disappointing.
Researchers at Cincinnati Children's report that in their mouse study, deleting miR-219 seemed to produce a “surge” of Lingo 1. That said, there is some work to be done before a synthetic miR-219 treatment is ready for human trials. Lu and his colleagues are perfecting their formulation of the microRNA to ease its delivery, according to the release. They also plan to test their approach in other models of neurological diseases.