Your browser doesn't support javascript.
loading
Death after High-Dose rAAV9 Gene Therapy in a Patient with Duchenne's Muscular Dystrophy.
Lek, Angela; Wong, Brenda; Keeler, Allison; Blackwood, Meghan; Ma, Kaiyue; Huang, Shushu; Sylvia, Katelyn; Batista, A Rita; Artinian, Rebecca; Kokoski, Danielle; Parajuli, Shestruma; Putra, Juan; Carreon, C Katte; Lidov, Hart; Woodman, Keryn; Pajusalu, Sander; Spinazzola, Janelle M; Gallagher, Thomas; LaRovere, Joan; Balderson, Diane; Black, Lauren; Sutton, Keith; Horgan, Richard; Lek, Monkol; Flotte, Terence.
Afiliação
  • Lek A; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Wong B; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Keeler A; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Blackwood M; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Ma K; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Huang S; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Sylvia K; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Batista AR; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Artinian R; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Kokoski D; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Parajuli S; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Putra J; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Carreon CK; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Lidov H; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Woodman K; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Pajusalu S; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Spinazzola JM; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Gallagher T; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • LaRovere J; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Balderson D; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Black L; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Sutton K; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Horgan R; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Lek M; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
  • Flotte T; From the Department of Genetics, Yale School of Medicine, New Haven (A.L., K.M., S.H., K.W., S. Pajusalu, M.L.), and Cure Rare Disease, Woodbridge (R.H.) - both in Connecticut; the Departments of Pediatrics (B.W., A.K., R.A., D.K., T.F.) and Neurology (A.R.B.) and Horae Gene Therapy Center and the L
N Engl J Med ; 389(13): 1203-1210, 2023 Sep 28.
Article em En | MEDLINE | ID: mdl-37754285
ABSTRACT
We treated a 27-year-old patient with Duchenne's muscular dystrophy (DMD) with recombinant adeno-associated virus (rAAV) serotype 9 containing dSaCas9 (i.e., "dead" Staphylococcus aureus Cas9, in which the Cas9 nuclease activity has been inactivated) fused to VP64; this transgene was designed to up-regulate cortical dystrophin as a custom CRISPR-transactivator therapy. The dose of rAAV used was 1×1014 vector genomes per kilogram of body weight. Mild cardiac dysfunction and pericardial effusion developed, followed by acute respiratory distress syndrome (ARDS) and cardiac arrest 6 days after transgene treatment; the patient died 2 days later. A postmortem examination showed severe diffuse alveolar damage. Expression of transgene in the liver was minimal, and there was no evidence of AAV serotype 9 antibodies or effector T-cell reactivity in the organs. These findings indicate that an innate immune reaction caused ARDS in a patient with advanced DMD treated with high-dose rAAV gene therapy. (Funded by Cure Rare Disease.).
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Síndrome do Desconforto Respiratório / Terapia Genética / Distrofina / Transgenes / Distrofia Muscular de Duchenne Limite: Adult / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Síndrome do Desconforto Respiratório / Terapia Genética / Distrofina / Transgenes / Distrofia Muscular de Duchenne Limite: Adult / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article