Death following high-dose AAV9 gene therapy in a patient with advanced SMA-PME

Molecular Therapy 2026 Open access

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Authors: Odile Boespflug‐Tanguy, Arnaud Valent, Jérôme Rambaud, Pierre-Louis Léger, Isabelle Plu, Danielle Seilhean, Véronique Frémeaux‐Bacchi, Thierry Levade, Martina Marinello, Jérôme Denard, Marion Derome, P. Brun
+14 more Nicolas Guerchet, Philippe Véron, Michael Blatzer, Romain Fragnoud, Laura Prieto, Tanguy Corbel, Nathalie Knuchel-Legendre, Beatrice Beaurain, Marielle Lelait, Manon Sanz, Katleen Abergel, Amanda Riviere, Ana Buj-Bello, Gérald Perret
DOI: 10.1016/j.ymthe.2026.05.016
Cited by: 1
References: 13

Abstract

vector genomes per kilogram of body weight was administered under prophylactic prednisolone and sirolimus. The patient experienced rapid onset of complement activation leading to cytokine-mediated capillary leak syndrome, culminating in refractory shock, multiorgan failure, and death on day 8. A postmortem examination revealed acute circulatory failure as the cause of death without myocarditis or thrombotic microangiopathy. Some endothelial injury was suggested by a rise in von Willebrand factor from days 4 to 8, paralleled by increased hyaluronic acid on days 7 and 8. These findings underscore the potential for life-threatening innate immune activation in patients with advanced SMA-PME receiving high-dose systemic AAV9 gene therapy, highlighting the need to identify high-risk patients and proactively monitor biomarkers of endothelial injury.

Fields of Study & Subjects

Neurogenetic and Muscular Disorders Research Virus-based gene therapy research Viral Infections and Immunology Research

Publication details

Journal / source
Molecular Therapy
Publisher
Elsevier BV
Volume
34
Issue
8
Pages
4442–4448
Publication date
26 May 2026
Language
EN