With CMTA’s support, researchers at San Raffaele Scientific Institute in Milan, Italy, led by Alessandra Bolino, PhD, are making significant progress in developing an AAV9-based genetic therapy for CMT4B1. This $380,000 CMTA Strategy To Accelerate Research (CMTA-STAR) investment is part of a broader effort to accelerate genetic therapies for less common, severe forms of CMT, including CMT4B2 and CMT4B3.
Targeting CMT4B1 with AAV9 Gene Therapy
CMT4B1 is a recessive form of CMT caused by mutations in the MTMR2 gene, leading to an absence of the MTMR2 enzyme. The lack of this enzyme disrupts Schwann cell function, impacting peripheral nerve myelin structure and peripheral nerve health, causing severe CMT symptoms and progression.
Dr. Bolino’s team is testing an AAV9-mediated approach to deliver a working MTMR2 enzyme to Schwann cells, with encouraging results. Early studies using a specialized CMT4B1 mouse model showed that this therapy successfully reached Schwann cells, an essential step in restoring normal peripheral nerve function.
Breakthrough Findings: Correcting Myelin Abnormalities
The latest findings provide encouraging evidence that AAV9-MTMR2 genetic therapy improves the peripheral nerve myelin defects characteristic of CMT4B1:
- Early tests showed successful delivery of MTMR2 to Schwann cells, critical for maintaining healthy peripheral nerve myelin.
- Researchers demonstrated that AAV9-mediated gene therapy reduces myelin outfoldings, a hallmark of CMT4B1-related nerve damage.
- Improvements in myelin structure indicate potential therapeutic benefit, supporting the next research phase.
Optimizing Genetic Therapy for Future Studies
To strengthen this approach, Dr. Bolino’s team has refined how the therapy is produced and delivered to Schwann cells, ensuring it reaches the right targets as efficiently as possible. They have now created a highly purified version of the AAV9-MTMR2 therapy, which they will test in upcoming studies to measure its long-term effects on nerve function and disease progression.
CMTA-STAR: Driving Genetic Therapy Research Forward
“Investing in gene therapy research for CMT4B1 is a critical step toward expanding treatment possibilities for the broader CMT community,” said Katherine Forsey, PhD, CMTA’s Chief Research Officer. “Through CMTA-STAR, we are not only advancing potential therapies for those with CMT4B1, but we are also paving the way for future genetic therapies that could transform treatment options for other recessive forms of CMT, including CMT4B2 and CMT4B3.”
Together, We Drive Progress
CMTA-STAR thrives because of the generosity and involvement of the CMT community. This research is 100% donor-funded by those who believe in a future without CMT and is powered by individuals who step forward to participate in research. Every scientific breakthrough, clinical study, and treatment discovery happens because of this shared commitment. Your support fuels progress and brings us closer to real solutions for CMT.
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Published on: April 3, 2025