The team presenting their research (from left): Professor Minseok Kim, PhD...
The team presenting their research (from left): Professor Minseok Kim, PhD student Aseer Intisar, PhD candidate Hyun Gyu Kang

Image source: DGIST

News • Electric stimulation instead of drug therapy

A new approach to treat Charcot-Marie-Tooth (CMT) Disease

A research team from the Korean Daegu Gyeongbuk Institute of Science & Technology (DGIST) develops an electronic medicine technology that restores abnormal protein behavior, the cause of Charcot-Marie-Tooth Disease (CMT).

The research team led by Professor Minseok Kim from the Department of New Biology at DGIST (President Yang Kuk) has developed a technology that can treat Charcot-Marie-Tooth disease, an incurable hereditary disease, with electric stimulation instead of drug therapy. The core of this technology is electric stimulation that restores the abnormal distribution of peripheral myelin protein 22 (PMP 22), the cause of the disease, to normal. The research team discovered it by conducting a series of electric stimulation experiments using a CMT disease subtype 1A (CMT1A) cell model. This technology has considerable potential for the development of an electronic medicine with minimal side effects in the future. 

The study was conducted with the support of the National Research Foundation of Korea and the results are published in the bioscience journal ‘Biosensors and Bioelectronics.’

We hope that new electric medicine technologies will soon be commercialized to address CMT disease that currently has no cure and causes suffering to millions of people worldwide

Minseok Kim

CMT disease causes muscle atrophy, numbness, foot deformities, paralysis, and other symptoms due to the loss of myelin sheath in peripheral nerves. It is a genetic disease that affects a large number of people, with approximately 1 in 2,500 individuals affected. However, there is currently no definitive treatment for this disease. CMT1A, a subtype of CMT disease, is among the most prevalent types of peripheral nerve damage worldwide and is caused by PMP22 overexpression in Schwann cells. PMP22 overexpression in Schwann cells causes the PMP22 protein to aggregate in the cells, ultimately leading to peripheral nerve damage. 

To address PMP22 overexpression, Professor Minseok Kim’s team developed a CMT1A cell model ‘PMP22-overexpressing schwannoma cell’. This team applied a high-speed electric stimulation screening platform to the cells to identify optimal stimulation conditions for effective therapeutic outcomes. This electric stimulation eliminated the PMP22 protein aggregation around the nucleus that occurs in CMT1A disease and restored the normal distribution of the PMP22 protein towards the cell membrane, similar to that of a normal Schwann cell. 

A schematic diagram of gene control related to the improvement and water...
A schematic diagram of gene control related to the improvement and water plantation of PMP22 intracellular aggregation by electrical stimulation of CMT Schuban cells

Image source: DGIST; from: Intisar et al.: Electroceutical approach ameliorates intracellular PMP22 aggregation and promotes pro-myelinating pathways in a CMT1A in vitro model; Biosensors and Bioelectronics 2023

In addition, the research team observed an increase in the expression of genes (e.g., MBP, MAG) that play an important role in the formation of myelin sheaths constituting a part of peripheral nerves and changes in the gene expression of transcription factors (Krox-20, Oct-6, c-Jun, and Sox10) that control myelin sheath formation, leading to the induction of myelination in the CMT1A cell model. 

Professor Minseok Kim from the Department of New Biology at DGIST stated that, “The key of this study is that it is the first demonstration that electric stimulation can restore the normal distribution of PMP22, which is a major protein in CMT1A disease.” He further expressed that, “We hope that new electric medicine technologies will soon be commercialized to address CMT disease that currently has no cure and causes suffering to millions of people worldwide.” 


Source: Daegu Gyeongbuk Institute of Science & Technology

03.04.2023

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