With CMTA support of $442,334, 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.
March 2026 Update
The Bolino lab evaluated a long-term oral treatment approach in a CMT4B1 mouse model to better understand its effects on nerve health over time. After six months of treatment, the team saw improvements in nerve function and reduced signs of peripheral nerve myelin degeneration.
However, this approach did not reduce the number of fibers with harmful myelin outfoldings in the peripheral nerves, a defining feature of CMT4B1. This contrasts with earlier preclinical studies using a different formulation and delivery method, which showed an effect on these structures.
These findings indicate that how these medicines are delivered, including dosage and formulation, may significantly influence their impact on different aspects of the disease. Ongoing work focuses on identifying combinations that best support both peripheral nerve function and myelin structure for future therapeutic development.
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.
CMTA’s Work Leads to Telethon Foundation Grant for Bolino
Data generated through this CMTA-supported project served as preliminary evidence in a successful grant application to the Telethon Foundation, which awarded Alessandra Bolino, PhD, a €350,000, three-year grant beginning in June 2026.
The Telethon Foundation is one of Europe’s leading private nonprofit funders of rare genetic disease research. Based in Italy and funded through public donations, it has supported biomedical research for more than 35 years through a rigorous, internationally peer-reviewed grant process with a track record of funding high-impact science across a broad range of rare conditions.
The Telethon grant will extend this line of research beyond the current CMTA project, supporting the continued development of gene therapy strategies for CMT4B. This award reflects the translational quality of the work CMTA has funded and its capacity to attract additional investment in CMT research.
