A Cypriot team has developed a new gene therapy called AAVrh10-hMPZ.GJB1 aimed at restoring connexin 32 expression in X-linked Charcot-Marie-Tooth disease (CMT X1) and tested it via intrathecal administration in a mouse model of the disease (Gjb1-null).
- The mice were divided into four groups: one receiving the control vector AAVrh10-hMPZ.EGFP and the other three the therapeutic vector at different doses (low, standard or high).
- The standard and high doses were associated with an improvement in muscle strength two and four months after injection.
- Sciatic nerve conduction velocity was also improved after four months with these doses, with a value identical to that of wild-type mice.
- These improvements were correlated with a high level of connexin 32 expression observed in the Schwann cells of mice treated with these doses.
- For mice treated with low doses, motor nerve conduction velocity was improved, but not functional results. The level of connexin 32 expression remained low.
- Six weeks after injection, gene therapy did not cause histological alterations or deleterious inflammation, but induced the production of anti-AAVrh10 antibodies at both standard and high doses.
This study provides proof of concept for this AAVrh10-mediated gene therapy approach in CMT X1.
