With CMTA support of $90,860, researchers led by Uri Manor, PhD, at the University of California, San Diego, are advancing therapeutic approaches for CMT2A by applying a deep learning-based Artificial Intelligence (AI) imaging platform to study organelle transport. In CMT2A, mutations in the MFN2 gene disrupt the mobility of mitochondria, the cell’s powerhouses, and lysosomes, the cell’s recycling centers. These small structures inside our cells (organelles, or “mini-organs” that perform vital jobs) must move efficiently to keep nerves healthy; when they stall, nerve function breaks down and disease progresses.
May 2026: Final Report
The Manor lab confirmed that CMT2A-causing mutations disrupt the movement and organization of both mitochondria and lysosomes in peripheral nerve cells. Because peripheral nerves are among the longest cells in the body, they depend on efficient, long-distance organelle transport to stay healthy. To measure these defects and test whether candidate treatments can fix them, Manor and his team built patient-derived nerve cell models and used the CMTA-developed CMT2A R364W rat model. These tools successfully captured how mitochondria split apart and rejoin (a process called fission and fusion) in CMT2A and can measure the faulty and healthy copies of the MFN2 gene separately. The team also showed that the R364W rat model reflects the nerve, motor, and limb changes seen in people with CMT2A, providing researchers with the confidence that findings in the lab can translate to patients.
With these tools in place, the team’s next step is to develop antisense oligonucleotides (ASOs), genetic medicines that work like a piece of Scotch tape placed over a faulty genetic instruction, blocking the cell from reading it. Already approved for several neurological diseases, ASOs offer a path to turn down the faulty copy of the MFN2 gene while leaving the healthy copy alone. Researchers believe this could improve nerve function, potentially alleviating CMT2A symptoms.
The patient-derived nerve cell models and R364W rat model now provide a clear path to screen ASO candidates, test whether they restore nerve cell health, and advance the strongest candidates toward future clinical development. This project moved CMT2A research from disease modeling to a practical therapeutic pipeline with a defined next step, bringing treatments closer to patients.
