Gene therapy shows promise for rare nerve disorder CMT1A
Researchers have identified a safe dosing range for an experimental gene therapy targeting CMT1A, a progressive nerve disorder affecting hundreds of thousands worldwide. Testing in animals suggests the treatment can reach damaged nerve cells and reduce disease-causing proteins to therapeutic levels—clearing a critical hurdle for human trials and potentially opening a market for genetic treatments of peripheral nerve diseases.
Originaltitel: Safety, efficacy, and distal nerve Schwann cell biodistribution in mice and NHPs to support translation of AAV9 RNAi therapy for CMT1A
, identified a safe and effective dosing range in mice, demonstrated absence of significant toxicity in rodents and non-human primates (NHPs), and performed a detailed AAV biodistribution study in a large animal model. We found vector biodistribution and miR871 expression in distal peripheral nerves, PMP22 target engagement in mice and NHPs, and silencing to levels expected to support normal myelination in humans. We identified the minimally efficacious to maximum tolerated dose range of AAV9.U6.miR871 in mice and confirmed safety range in NHPs for extrapolation to anticipated clinical trials. Our study supports the scale-up potential of gene therapy to treat CMT1A and other demyelinating peripheral neuropathies.