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Thrombotic microangiopathy following gene therapy for 5q-spinal muscular atrophy

Onasemnogene abeparvovec (OA) is the first gene replacement therapy (GT) approved for 5q spinal muscular atrophy (SMA). While effective, it can cause severe side effects, including thrombotic microangiopathy (TMA). The pathophysiology, risk factors, and management of viral-vector-related TMA remain...

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Hauptverfasser: Gontijo Camelo, Clara (VerfasserIn) , Mendonça, Rodrigo Holanda (VerfasserIn) , Moreno, Cristiane Araújo Martins (VerfasserIn) , Ferreira, Juliana Caires Oliveira Achili (VerfasserIn) , Ortega, Adriana Banzzatto (VerfasserIn) , van der Linden, Vanessa (VerfasserIn) , Campos, Rejane Souza Macedo (VerfasserIn) , van der Linden, Helio (VerfasserIn) , da Cunha, Natalia Spinola Costa (VerfasserIn) , Gurgel-Giannetti, Juliana (VerfasserIn) , Chaves, Janaina Monteiro (VerfasserIn) , Miranda, Silvana Maria Carvalho (VerfasserIn) , Ziegler, Andreas (VerfasserIn) , Zanoteli, Edmar (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 19 June 2025
In: Gene therapy
Year: 2025, Pages: 1-5
ISSN:1476-5462
DOI:10.1038/s41434-025-00545-6
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41434-025-00545-6
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41434-025-00545-6
Volltext
Verfasserangaben:Clara Gontijo Camelo, Rodrigo Holanda Mendonça, Cristiane Araújo Martins Moreno, Juliana Caires Oliveira Achili Ferreira, Adriana Banzzatto Ortega, Vanessa van der Linden, Rejane Souza Macedo Campos, Helio van der Linden, Natalia Spinola Costa da Cunha, Juliana Gurgel-Giannetti, Janaina Monteiro Chaves, Silvana Maria Carvalho Miranda, Andreas Ziegler, Edmar Zanoteli
Beschreibung
Zusammenfassung:Onasemnogene abeparvovec (OA) is the first gene replacement therapy (GT) approved for 5q spinal muscular atrophy (SMA). While effective, it can cause severe side effects, including thrombotic microangiopathy (TMA). The pathophysiology, risk factors, and management of viral-vector-related TMA remain unclear. This study aimed to evaluate TMA frequency among Brazilian patients treated with OA and characterize their clinical and laboratory profiles. This retrospective, multicenter study analyzed 294 Brazilian patients with 5q SMA treated with OA between October 2020 and September 2024, of whom seven (2.4%) developed TMA. The average age at OA administration was 20.4 months, and the average weight was 11.5 kg. Three patients had documented infections before OA administration. TMA symptoms appeared within 6-10 days post-infusion. All patients showed hemolytic anemia, thrombocytopenia, and at least one organ dysfunction. Treatment included plasmapheresis in two cases and increased corticosteroid doses in four cases. One patient died from TMA complications. Whole exome sequencing in five patients identified no pathogenic variants linked to TMA. TMA is a rare but severe complication of OA therapy for SMA. Prompt recognition and management, often with corticosteroids, are crucial for improving outcomes.
Beschreibung:Online veröffentlicht: 19. Juni 2025
Gesehen am 24.10.2025
Beschreibung:Online Resource
ISSN:1476-5462
DOI:10.1038/s41434-025-00545-6

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