Dr. Chris Lorson and the team at Shift Pharmaceuticals are testing a gene targeting approach to decrease the levels of PMP22 protein which is known to cause CMT1A. They are developing and analyzing a new series of morpholino-based antisense oligonucleotide drugs (PMO ASOs). The key advantages of PMO ASOs are their low toxicity compared to other gene therapy approaches and their ability to target Schwann cells, the cells that produce myelin in the peripheral nerves.

In their CMT Research Foundation-funded studies, they first showed in cells that the PMO ASOs reliably reduced the expression of PMP22. They next took the most effective PMO ASO and tested it in mice genetically engineered to express too much PMP22 – “CMT1A mice” – with promising results. As expected, CMT1A had serious deficiencies in movement and balance, as measured by the fact that it took them much longer than healthy mice to traverse a fixed-length beam in a beam-walking task. However, treatment with Shift’s PMO ASO greatly reduced the traversal time to levels near those of healthy animals. Moreover, this effect held regardless of whether the CMT1A mice were treated within days of birth or treated closer to the age that symptoms first arise.