Gene therapy is a promising approach for possible treatments and cures for Charcot-Marie-Tooth disease. However, a key challenge is how to deliver these therapies effectively to the cells of the peripheral nervous system.

A potential solution to this was explored by Dr. James Dahlman, PhD, in his recently completed CMTRF-funded project, which focused on generating optimized versions of a type of gene therapy delivery technology, called lipid nanoparticles, that have improved delivery to the myelinating Schwann cells of the peripheral nerves. Dr. Dahlman previously developed lipid nanoparticles that have improved delivery to other tissue types.

Although peripheral nerves are difficult to target, Dr. Dahlman used advanced techniques to confirm that the lipid nanoparticles reached their intended cells. He also demonstrated successful delivery to the brain, which is promising because brain tissue behaves similarly to peripheral nerve tissue. This finding suggests the approach could be adapted to target the peripheral nervous system.

Dr. Dahlman is developing a new technique to improve this approach and enable screening to take place in nerves, thus opening the door to targeting the peripheral nervous system.

These advancements in optimizing lipid nanoparticles for gene therapy delivery could also advance brain targeting methods and be adapted for further exploration in peripheral nerves. Overall, Dr. Dahlman’s work paves the way for new strategies to deliver therapies for CMT.