Molecular Therapy Sparks Remyelination, Hope for MS Cure

An experimental treatment was able to restore myelin on peripheral nerves in mice, according to a study published by Nature Medicine. The treatment was also observed to improve limb function and reduce discomfort.

These findings suggest the therapy may provide an effective treatment for individuals with multiple sclerosis (MS) who experience serious adverse events and pain related to demyelination, according to the study authors. Despite other studies that have outlined potential remyelinating therapies, there are currently no effective treatments for MS and other demyelinating diseases.

To evaluate potential treatments, the researchers conducted a small-molecule epigenetic screening to search for drugs that inhibit enzymes that cause chromosome alterations. These mutations change how cellular gene activity is regulated and impact myelin regeneration.

The researchers then tested small molecule inhibitors used for cancer in mice with injured sciatic nerves. The compounds target the histone deacetylase 3 (HDAC3) enzyme, which has been shown to inhibit remyelination on peripheral nerves, according to the authors.

“Remarkably, temporary inhibition of HDAC3 robustly accelerated the formation of myelin that helps insulate peripheral nerves,” said principal investigator Q. Richard Lu, PhD. “This promoted functional recovery in the animals after peripheral nerve injury.”

Normal HDAC3 is tasked with controlling the production of myelin by Schwann cells; however, after peripheral nerve injury, the enzyme causes epigenetic changes to chromosomes and gene regulation that restrict myelin regeneration, according to the study. The resulting myelin is faulty and can block or slow signals from the central nervous system to the rest of the body, resulting in disability and other hallmark characteristics of MS.

The mice were treated with HDAC3 inhibitors only during a critical phase of nerve regeneration. The authors discovered that administering the treatment within that time frame resulted in the amount of remyelination that is needed to restore function, according to the study.

The authors said that timing is crucial for this therapy and that inhibiting HDAC3 for too long results in myelin that is excessively thick. Overgrown myelin may also result in functional problems for patients.

Since the enzyme blockade was successfully tested in mice, the researchers are currently looking into other animal models that can more closely replicate peripheral nerve repair in humans.

Further research is needed, especially regarding demyelinating diseases such as MS, but the findings provide hope of a cure for demyelinating diseases, according to the study. The authors also noted that they plan to test potential dosing levels that could translate to clinical trials of human patients with myelin deficiencies.