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.
September 2025 Update
Dr. Manor’s team built and validated this imaging system to create detailed “videos” of organelle movement in patient-derived nerve cells. The work confirmed that mitochondria and lysosomes become stalled in CMT2A neurons, revealing how MFN2 mutations disrupt the transport system that keeps nerves healthy. They also discovered that the faulty MFN2 protein unexpectedly accumulates at lysosomes, providing a new clue about how the disease causes damage.
The same defects were found in a CRISPR-developed model of CMT2A, which also showed reduced grip strength, closely matching the patient experience. With these models in place, the researchers are now preparing to test candidate therapies, including mitofusin agonists and allele-specific siRNA (a genetic tool that selectively “turns off” faulty genes), to determine whether restoring organelle transport can improve nerve health.
