Death following high-dose AAV9 gene therapy in a patient with advanced SMA-PME - PubMed
3 hours ago
- #Pharmacovigilance
- #SMA-PME
- #AAV9 gene therapy
- First-in-human IV AAV9 gene therapy (GNT-017-ASAH-CU) administered to a 15-year-old female with advanced SMA-PME caused by ASAH1 mutations.
- High-dose therapy (2.2×10^14 vg/kg) led to rapid complement activation, cytokine-mediated capillary leak syndrome, refractory shock, multiorgan failure, and death on day 8.
- Postmortem findings showed acute circulatory failure without myocarditis/thrombotic microangiopathy, with elevated von Willebrand factor and hyaluronic acid suggesting endothelial injury.
- Highlights risk of life-threatening innate immune activation in advanced SMA-PME with systemic AAV9, underscoring need for identifying high-risk patients and monitoring endothelial biomarkers.