With combined support totaling $102,968 from CMTA, Shark Tooth Bio, and the National Research Council Canada (NRC), a team of researchers led by Umar Iqbal, PhD, is conducting a study to develop and test a targeted delivery system designed to help RNA medicines (a type of genetic therapy) reach Schwann cells in CMT1A. Getting medicines to Schwann cells remains a central challenge in CMT.
Peripheral nerve cells are protected by specialized biological barriers, such as the blood–nerve barrier, which not only keep out harmful foreign substances but also medicines meant to help. This project focuses on engineering and testing peptide-LNP systems (tiny mail carriers) to deliver RNA medicines to Schwann cells (the specialized cells in peripheral nerves that make peripheral nerve myelin).
Iqbal and his team will use cellular studies in CMT models to assess delivery to peripheral nervous system tissues, how effectively RNA medicines enter Schwann cells, and whether target engagement can be detected in CMT1A models.
The goal of this work is to determine whether this delivery approach is suitable for further development and to generate data that can guide future research focused on RNA-based medicines for CMT1A.
June 2026 Update
The Iqbal lab has now tested five different peptide-targeting molecules attached to lipid nanoparticles (LNPs) to determine which most effectively delivers RNA medicines into Schwann cells. Using mouse Schwann cells, the team identified one peptide that achieved the strongest uptake, with two additional candidates also showing promising delivery performance.
The researchers then evaluated whether these targeted delivery systems could reduce PMP22 levels, the protein overexpressed in CMT1A. Two peptide-LNP combinations reduced PMP22 protein levels by approximately 30%, demonstrating successful delivery of the RNA medicine into Schwann cells and measurable target engagement.
Iqbal reports that one of the lead peptide candidates mimics a natural interaction between nerve fibers and Schwann cells, helping maintain healthy nerve structure. Based on these findings, the team plans to advance the lead peptide candidate into additional CMT1A validation studies to further evaluate its ability to deliver RNA medicines to Schwann cells and reduce PMP22 levels.
