New technologies in gene editing such as CRISPR/Cas9 present a promising opportunity for the treatment of genetic diseases like CMT at the root cause – often just a single base pair or “letter” change in the DNA sequence. Research lead by Dr. Bruce Conklin and Dr. Luke Judge used these gene editing technologies to specifically “delete” the disease genes that cause CMT while preserving the normal copy of the gene. They are focusing on genes where a single normal gene copy is adequate to support normal function, allowing them to delete just the disease copy of the gene.

The approach can be applied to many different types of CMT, and for their initial studies, they focused on the genes that cause CMT2A and CMT2E (MFN2 and NEFL).

To develop their gene editing technology, they used induced-pluripotent stem cells (iPSC) from CMT patients often referred to as “disease in a dish” experiments. Patient iPSC are ideal for these studies, since they contain the complete genetic sequence of the patient and can be converted into various types of neurons that mimic the disease process.

They have already shown that it is possible to specifically delete the disease-causing genes for different mutations in MFN2 and NEFL, and in the case of NEFL that the strategy was able to “cure” the treated neurons in the laboratory. The researchers are continuing to refine the strategy to make it as safe and effective as possible for the largest number of CMT patients. In parallel, they are developing methods to deliver gene editing directly to nerves in the body, and testing the approach in a mouse model of CMT2E.

Published:November 30, 2023