With CMTA support of $380,000, researchers led by Alessandra Bolino, PhD, at the San Raffaele Scientific Institute in Milan, Italy, are advancing AAV9-based genetic therapy to treat CMT4B1, a recessive type of CMT caused by mutations in the MTMR2 gene.
Using a specialized mouse model of CMT4B1, the research team has generated new data demonstrating that AAV9-mediated MTMR2 replacement improves the peripheral nerve myelin abnormalities characteristic of CMT4B1. Early studies confirmed that this approach effectively delivers MTMR2 to Schwann cells, essential for maintaining healthy peripheral nerve myelin. The latest findings show that treatment with AAV9-MTMR2 reduces myelin outfoldings, a hallmark of CMT4B1, providing further evidence of its therapeutic potential.
The team has also optimized the viral vector production process to enhance gene delivery efficiency and ensure reproducibility in future studies. In upcoming experiments, a newly acquired high-purity AAV9-MTMR2 preparation will be tested to assess its long-term effects on peripheral nerve function and CMT4B1 disease progression. These advances mark important progress toward developing genetic therapy for CMT4B1 and potentially other forms of CMT.
September 2025 Update
The team has obtained robust preliminary data in a CMT4B1 mouse model showing that AAV9-mediated delivery of MTMR2 can correct the abnormal myelin changes that characterize this CMT subtype. These findings build on earlier success demonstrating efficient targeting of Schwann cells and provide stronger evidence that gene replacement can address the root cause of CMT4B1.
With this foundation, the researchers are continuing preclinical studies to evaluate how restoring MTMR2 affects nerve health and function over time. This work marks steady progress toward a potential genetic therapy for CMT4B1 and may also inform strategies for other CMT4 subtypes, such as 4B2 and 4B3.
