The CMT Research Foundation announce a new project with Samsara Therapeutics, a US/UK-based biotech company that is developing a novel class of drugs for CMT1A.
CMT1A is caused by duplication of a stretch of DNA that includes the PMP22 gene, and people with CMT1A produce approximately 33% more PMP22 protein than people who do not have CMT1A. While the mechanism of disease is not known precisely, this overproduction of PMP22 impedes the normal inclusion of PMP22 in the myelin sheath produced by Schwann cells in the peripheral nerves, leading eventually to demyelination, axon loss, and disability. One hypothesis about how PMP22 gene duplication causes CMT1A is that the extra PMP22 protein clumps together to form aggregates that are toxic to the peripheral nerves. And in fact, PMP22 aggregates have been found in the nerve cells of CMT1A model mice who are genetically engineered to overproduce PMP22.
Samsara Therapeutics has discovered a number of drug-like molecules called autophagy enhancers that stimulate the body’s natural autophagy process – the breaking down and recycling of damaged or dysfunctional proteins. In an early preclinical study, they showed that this class of drugs improves outcomes in CMT1A model mice, reducing PMP22 protein levels and restoring measures of nerve structure and function.