Previous research from Dr. Alessandra Bolino demonstrated that inhibiting a protein called PIKfyve kinase could ameliorate some disease characteristics in CMT4B1 cells. In this project, Dr. Bolino partnered with AcuraStem to test one of their PIKfyve inhibitor drug candidates in both cell and animal models of CMT4B1.

This project has completed, and the results showed that AcuraStem’s PIKfyve inhibitor significantly reduced the number of abnormal myelin fibers in CMT4B1 cells. However, when tested in the CMT4B1 mouse model, the compound did not improve disease characteristics. It is possible that higher dose levels are needed to see a benefit with this molecule but, unfortunately, it was not possible to test higher dose levels due to poor solubility of the compound. Despite the negative findings and challenges with the drug properties of the compound, this project still provided valuable insights that have led the team toward more promising therapeutic options to explore. The researchers remain committed to exploring therapeutic avenues for CMT4B1 and related neuropathies.