Positive results in mice for a new gene therapy for type I SMA

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 IAu cours d’un essai clinique de phase I un médicament dont l’intérêt thérapeutique a été montré sur des modèles animaux et/ou cellulaires (essais précliniques) est administré pour la première fois à un petit groupe de volontaires sains, plus rarement à des malades, afin d’évaluer leur tolérance à la substance en fonction de la dose (Comment le futur traitement est-il absorbé et éliminé ? Comment se fait sa répartition dans les organes ? Est-il toxique et à quelles doses ? Existe-t-il des effets secondaires ?)./II trial underway, these results support the continued clinical development of EXG001-307.

Efficacy and preliminary safety assessment of EXG001-307 AAV gene therapy for spinal muscular atrophy. Song C, Wang Q, Zhu P et al. Mol Ther Methods Clin Dev. 2025 Apr.