Foundation Extends Funding for CMT1A Gene Therapy Study

The CMT Research Foundation will grant additional funding to a project investigating a potential gene therapy to reduce the elevated levels of the protein PMP22 that cause Charot-Marie-Tooth type 1A (CMT1A). 

The funding will help support preclinical development of the therapy, led by Kleopas Kleopa, MD, at the Cyprus Institute of Neurology and Genetics, as well as potential clinical trials, according to a press release. 

In addition to the gene therapy study, Kleopa’s research team also will be exploring potential biomarkers for CMT, including neurofilament light chain (NfL) and other blood and skin markers that could be used to monitor CMT disease progression and the effectiveness of experimental treatments. Notably, NfL levels are typically elevated in response to nerve cell damage, representing a potential biomarker for diseases of the nervous system. 

The most common CMT subtype, CMT1A is a group of genetic disorders of the peripheral nerves that connect the brain and spinal cord to the rest of the body.

CMT1A is caused by having an extra copy of the PMP22 gene, which provides instructions for making the PMP22 protein. PMP22 is involved in myelination, a process in which nerve cell  projections that extend to the muscles are wrapped in a protective coating of myelin, a fatty substance that facilitates the proper transmission of signals throughout the nervous system. The extra copy of the PMP22 gene results in elevated levels of PMP22 protein and myelin abnormalities and dysfunction.

The gene therapy project was developed based on the hypothesis that reducing levels of PMP22 protein would reduce myelin dysfunction and potentially rescue nerve damage in people with CMT1A. 

The CMT Research Foundation began funding the project in 2019. Kleopa and his team designed and tested several genetic sequences in a mouse model of CMT1A. Results showed that the gene therapy candidate reduced PMP22 protein levels in the sciatic nerve within one month, while also improving nerve structure, and increasing muscle strength and motor skills over a four-month treatment. Similar findings were seen in young and older animals.

Along with two collaborators, Kleopa was also the recipient of a grant from the Charcot–Marie–Tooth Association to develop gene therapies for CMT1A, CMT4 and CMTX.