Charcot-Marie-Tooth type 1B is caused by mutations myelin protein zero, which is an essential component making myelin, the protective layer or sheath around nerves. Defective myelin protein zero results in damaged or impaired myelin leading to progressive nerve damage and CMT1B symptoms. Dr. Afrooz Rashnonejad’s lab is developing a novel gene therapy approach to treat CMT1B, called “knockdown and replace”, that aims to reduce the mutant myelin protein zero and replace it with a healthy version.

Dr. Rashnonejad and her team have designed and tested several gene therapy candidates in cell culture models of CMT1B and successfully demonstrated that their myelin protein zero “knockdown and replace” strategy can decrease the amount of defective myelin protein zero while increasing the levels of healthy myelin, leading to enhanced formation of myelin sheaths around neurons and other improvements in the cells. This gene therapy approach also showed no apparent negative side effects on the treated cells. Together, these results demonstrate that this novel gene therapy could be an effective treatment for CMT1B. Next steps for this project include testing the effectiveness of this gene therapy approach in CMT1B mouse models and conducting additional tests to determine the optimized approach for the gene therapy.

Update as of September 2024: Dr. Rashnonejad presented the most recent findings from this project at the 2024 Global CMT Research Convention. The presented data included exciting results on the effect of the gene therapy in CMT1B mice, which are guiding the ongoing optimization efforts.