Electrical Stimulation Lowers Protein Clumps, Aids Myelin: CMT1A Model
Lab study proposes hourlong stimulation at 20 hertz as CMT1A treatment
Electrical stimulation reduced toxic PMP22 protein clumping and promoted myelin-making activity in a cell model of Charcot-Marie-Tooth disease type 1A (CMT1A), a new study reports.
“We expect that the findings … will play a significant role in the potential clinical translation of an electroceutical [electricity-based] treatment for CMT1A disease,” its researchers wrote.
The study, “Electroceutical approach ameliorates intracellular PMP22 aggregation and promotes pro-myelinating pathways in a CMT1A in vitro model,” was published in the journal Biosensors and Bioelectronics.
Tests done in Schwann cells overexpressing the PMP22 protein
CMT1A, the most common type of CMT, is caused by duplication of the gene that provides instructions for making the PMP22 protein. The excessive PMP22 protein that results forms toxic aggregates or clumps inside of cells.
Like other CMT types, CMT1A is characterized by the loss of myelin — the fatty wrapping around nerve fibers that helps them send electric signals — in the peripheral nervous system (outside the brain and spinal cord). Schwann cells, the cells responsible for making myelin in the peripheral nervous system, are particularly vulnerable to toxic PMP22.
Recent studies have suggested that applying gentle electrical stimulation to cells of the peripheral nervous system can help to promote growth and myelin repair, but the molecular mechanisms of these effects remain poorly understood.
A team of scientists in Korea investigated the effects of electrical stimulation in a Schwann cell line that had been engineered to overexpress PMP22 protein, an in vitro (using cells in dishes) model of CMT1A.
Results showed that electrical stimulation reduced the amount of PMP22 clumps inside of the cells, instead prompting the protein to move toward the cell membrane as it normally does. The most potent effect was seen at a stimulation setting of 20 hertz (Hz).
“Our data showed that 20 Hz for 1 [hour] to PMP22-overexpressed Schwannoma cells reduced intracellular aggregation of PMP22 and promoted its distribution in the cell membrane,” the researchers wrote, suggesting that electrical stimulation “could be a prospective treatment option for CMT1A.”
Further analyses indicated that electrical stimulation led to significant increases in the activity of genes coding for key myelin-related proteins by the cells, specifically myelin basic protein and myelin-associated glycoprotein.
Electrical stimulation also promoted gene activity coding for several pro-myelinating transcription factors — proteins that regulate cellular activity by controlling which genes are “turned on or off” — and induced pro-myelinating molecular pathways.
“Altogether, we could conclude that 20 Hz for 1 [hour] not only ameliorated the PMP22 localization abnormality, but also induced a pro-myelinating effect in the in vitro CMT1A model,” the scientists wrote.