Ohio researchers have a novel microRNA treatment.
Researchers from Cincinnati Children’s Hospital say they have succeeded in partially restarting myelin generation in mice using a novel microRNA treatment.
The research could prove to be helpful in slowing down or reversing multiple sclerosis, a disease in which the protective myelin that covers nerve axons and speeds electrical transmissions is damaged.
It was already known that microRNA plays a role in the creation of oligodendrocytes, which in turn create the myelin “sheath.” The question for the Cincinnati team was whether therapeutic injection of certain microRNA would cause a reinvigoration of myelin creation. The researchers decided to look at one specific microRNA, miR-219, because earlier research has suggested the microRNA is absent in patients with neurodegenerative diseases like multiple sclerosis. When the scientists injected mice with miR-219, the results were exactly what they had hoped for.
“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 Q. Richard Lu, PhD, lead investigator on the study.
The mice in Lu’s study had myelin damage due to the chemical lysolecithin or due to induced autoimmune encephalomyelitis. The latter is the common mouse model for MS. The researchers injected miR-219 into the spinal columns and cerebrospinal fluid of the mice. After the miR-219 injections, they noted improved function of oligodendrocytes, leading to partial remyelination. Lu said this is a positive sign that miR-219 might be a solid therapeutic pathway.
“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” said Lu, the scientific director of the Brain Tumor Center at Cincinnati Children’s Hospital.
The researchers also learned more about the role of another microRNA, miR-338, which seems to have an impact on the myelination process.
“Further deletion of miR-338 exacerbates the miR-219 mutant hypomyelination phenotype,” the authors wrote. “Conversely, miR-219 overexpression promotes precocious oligodendrocyte maturation and regeneration processes in transgenic mice.”
However Lu cautioned in a press release that mice models are different than humans, so there is still a long way to to go before scientists will be able to say whether the miR-219 therapy has the same impact on human MS patients.
The next step in that journey will be to develop additional miR-219 mimics that can be safely delivered into brain tissue.
The Cincinnati research is one of a number of recent studies that have attempted to find successful pathways to myelin regeneration. Most recently, a study out of Northern Ireland looked at the role of regulatory T cells in generating myelin. It found regulatory T cells could enable myelination. However, as with the Cincinnati study, the Irish research was based was an early stage effort that has yet to be borne out in human subjects.
The study, titled “miR-219 Cooperates with miR-338 in Myelination and Promotes Myelin Repair in the CNS” was published March 27 in the journal Developmental Cell. The study can be read online here.