Gene editing as a therapeutic tool for treating disease has been very much in the news recently.  The most commonly used gene editing tool to permanently fix the underlying genetic cause of a disease is CRISPR/Cas9. A recent paper demonstrates the first proof-of-concept of gene editing in the peripheral nervous system.  The authors tested gene editing in a mouse model of CMT1A.  In patients with CMT1A, a region of DNA is duplicated which includes the PMP22 gene. Increased levels of PMP22 lead to demyelination of peripheral nerves and altered nerve function leading to sensory changes and muscle weaknesses.   The mouse model is engineered to express increased levels of human PMP22 and also displays peripheral nerve abnormalities very similar to what is observed in humans.

The authors targeted the gene editing tool to a region of the PMP22 gene that controls how much PMP22 is produced in peripheral nerves.  By injecting the sciatic nerve of the CMT1A mice once with the gene editing tool, the levels of PMP22 were significantly decreased.  If gene editing was performed before the mice displayed disease symptoms, significant improvements were observed in the structure of peripheral nerves as well in nerve function.  However, if gene editing was performed after the mice already displayed disease symptoms, less benefit was observed.  In neither case did disease correction reach that seen in normal mice.

While it’s exciting to see the power of gene editing brought to bear on CMT, additional work is required to increase the efficiency and safety of this technique before it can be tested in people.

by Grace Pavlath, PhD, Chief Science Officer for the CMT Research Foundation