While Zolgensma® gene therapy in SMA is associated with a risk of cardiotoxicity and hepatotoxicity, another gene therapy EXG001-307 could represent a new, safer option for patients with type I SMA. Results obtained by an American and Chinese team in a mouse model of SMA show :
- a dose-dependent efficacy of EXG001-307, with increased survival, weight gain and restoration of motor function in mice.
- a median survival time of 191 days with the highest dose of EXG001-307, compared with 32.5 days with the intermediate dose of the reference product scAAV9-CB-hSMN (identical design to Zolgensma®), the highest dose being toxic. Maximum survival was 319 days versus 124 days respectively.
- EXG001-307 was associated with reduced transgenic expression of SMN in the heart compared with the reference vector, leading to a better safety profile.
- Reduced cardiac and hepatic toxicities were observed in mice treated with EXG001-307, with no deaths, whereas mortality was high in mice treated at medium and high doses with scAAV9-CB-hSMN.
With a phase I/II trial underway, these results support the continued clinical development of EXG001-307.
