MicroRNA treatment restores nerve insulation, limb function in mice with multiple sclerosis

March 27, 2017, Cincinnati Children's Hospital Medical Center
The restored presence of proteins indicating myelin reformation (shown in red) in the lumbar spinal cord of a mouse treated with miR-219 mimic after injury to its central nervous system. Researchers report March 27 in Developmental Cell that treatment with the micro-RNA partially restored damaged nerves and limb function in mice. Credit: Cincinnati Children's

Scientists partially re-insulated ravaged nerves in mouse models of multiple sclerosis (MS) and restored limb mobility by treating the animals with a small non-coding RNA called a microRNA.

In a study published online March 27 in Developmental Cell, researchers at Cincinnati Children's Hospital Medical Center report that treatment with a microRNA called miR-219 restarted production of a substance called in nerves of the central nervous system. Myelin forms a protective sheath around nerves, allowing them to efficiently transmit electrical impulses that stimulate movement.

Study authors administered miR-219 into the spinal columns and cerebrospinal fluid of mice with coatings damaged by a chemical called lysolecithin or by autoimmune encephalomyelitis induced in the animals, which is used to MS. Treatment with miR-219 reinvigorated the function of damaged cells called oligodendrocytes that produce myelin, which allowed the substance to reform and reinsulate nerves.

"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 and scientific director of the Brain Tumor Center at Cincinnati Children's. "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."

The authors stress that because their study was conducted in laboratory mouse models of disease, their data cannot at this stage be applied to clinical treatment in humans.

Lu's laboratory studies how certain glial cell subtypes of the central and peripheral nervous system form, participate in regeneration and how they can transform into cancerous cells.

Molecular Silencer

MicroRNAs are short segments of RNA encoded on the chromosomes of cells. They regulate gene expression in cells by acting as molecular silencers, essentially blocking gene expression in certain situations.

A number of earlier research papers have pointed to the absence of miR-219 in the damaged nerves and tissues with certain neurodegenerative diseases like multiple sclerosis.

Lu and his colleagues tested the presence and effects of miR-219 in genetically-engineered mouse models of MS with chemically induced nerve coating damage by lysolecithin and autoimmune encephalomyelitis. They also deleted miR-219 in mice to test the impact this had on myelin-forming oligodendrocyte .

The absence of miR-219 allowed a surge of activity by several inhibitors of nerve re-myelination - including a protein called Lingo1. Further testing revealed that miR-219 is an essential part of a network that targets and blocks molecules that inhibit the ability of oligodendrocytes to form myelin.

This prompted the researchers to test treatment with miR-219 in their animal models. For this they used a miR-219 mimic - essentially a synthesized version of the microRNA. After administering the mimic to their mouse models, the researchers noted improved limb function and regeneration of the myelin coating on nerves.

Next steps

Lu and his colleagues are now trying to develop additional mimics of miR-219 and therapeutically effective formulations of the microRNA to ease its delivery - particularly into brain tissue. The researchers also continue to test the potential effectiveness of miR-219 in different models of neurodegenerative disease.

Explore further: Study hints at regeneration of nerve insulation to treat CHARGE birth defects

Related Stories

Study hints at regeneration of nerve insulation to treat CHARGE birth defects

February 29, 2016
Research in Nature Neuroscience suggests the possibility of treating a group of genetic birth defects with molecular therapy that would regenerate malformed nerve insulation in the central nervous system.

Schwann cells 'dine in' to clear myelin from injured nerves

July 6, 2015
Researchers reveal how cells in the peripheral nervous system (PNS) degrade myelin after nerve injury, a process that fails to occur in the central nervous system (CNS). The study appears in The Journal of Cell Biology.

New clues to myelination could help identify ways to intervene in neurodegenerative diseases

December 8, 2016
Researchers at the University at Buffalo have identified a critical step in myelination after birth that has significance for treating neurodegenerative diseases like multiple sclerosis, in which myelin is lost or damaged. ...

Elucidation of the molecular mechanisms involved in remyelination

September 3, 2015
Researchers in Japan have revealed the molecular mechanism involved in the process of repair to damage of the myelin sheath.

Enzyme in myelination process could lead to better understanding of neurological disorders

April 14, 2016
The removal of the enzyme Dnmt1 during oligodendrocyte progenitor cell (OPC) differentiation in the central nervous system resulted in inefficient myelin formation and neurological deterioration, including loss of control ...

Recommended for you

New technique helps uncover changes in ALS neurons

June 22, 2018
Northwestern Medicine scientists have discovered that some neurons affected by amyotrophic lateral sclerosis (ALS) display hypo-excitability, using a new method to measure electrical activity in cells, according to a study ...

Broken shuttle may interfere with learning in major brain disorders

June 22, 2018
Unable to carry signals based on sights and sounds to the genes that record memories, a broken shuttle protein may hinder learning in patients with intellectual disability, schizophrenia, and autism.

Watching stem cells repair spinal cord in real time

June 22, 2018
Monash University researchers have restored movement and regenerated nerves using stem cells in zebra fish where the spinal cord is severely damaged.

Scientists discover fundamental rule of brain plasticity

June 21, 2018
Our brains are famously flexible, or "plastic," because neurons can do new things by forging new or stronger connections with other neurons. But if some connections strengthen, neuroscientists have reasoned, neurons must ...

Waking up is hard to do: Prefrontal cortex implicated in consciousness

June 21, 2018
Philosophers have pondered the nature of consciousness for thousands of years. In the 21st century, the debate over how the brain gives rise to our everyday experience continues to puzzle scientists. To help, researchers ...

Researchers find mechanism behind choosing alcohol over healthy rewards

June 21, 2018
A new study links molecular changes in the brain to behaviours that are central in addiction, such as choosing a drug over alternative rewards. The researchers have developed a method in which rats learn to get an alcohol ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.