Adeno-associated virus serotype 9 antibody seroprevalence for patients in the United States with spinal muscular atrophy.

Autor:	Day JW; Department of Neurology, Stanford University Medical Center, Stanford, CA, USA., Mendell JR; Center for Gene Therapy, Nationwide Children's Hospital, Columbus, OH, USA.; Department of Pediatrics and Department of Neurology, The Ohio State University, Columbus, OH, USA., Burghes AHM; Department of Neurology and Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH, USA., van Olden RW; Novartis Gene Therapies Switzerland GmbH, Rotkreuz, Switzerland., Adhikary RR; CONEXTS-Real World Evidence, Novartis Healthcare Private Limited, Hyderabad, India., Dilly KW; Novartis Gene Therapies, Inc., Bannockburn, IL, USA.
Jazyk:	angličtina
Zdroj:	Molecular therapy. Methods & clinical development [Mol Ther Methods Clin Dev] 2023 Sep 20; Vol. 31, pp. 101117. Date of Electronic Publication: 2023 Sep 20 (Print Publication: 2023).
DOI:	10.1016/j.omtm.2023.101117
Abstrakt:	Onasemnogene abeparvovec is a recombinant adeno-associated virus serotype 9 (AAV9) vector-based gene therapy for spinal muscular atrophy (SMA). Patients with elevated titers of anti-AAV9 antibodies (AAV9-Ab) should not receive onasemnogene abeparvovec because of potential safety and efficacy implications. We conducted a retrospective study to describe the seroprevalence of anti-AAV9 binding antibodies for pediatric patients with SMA in the United States. At initial testing, 13.0% (115 of 882) of patients (mean [SD] age, 26.29 [33.66] weeks) had elevated AAV9-Ab titers. The prevalence of elevated titers decreased as age increased, with 18.2% (92 of 507) of patients ≤3 months old but only 1.1% (1 of 92) of patients ≥21 months old having elevated titers. This suggests transplacental maternal transfer of antibodies. No patterns of geographic variations in AAV9-Ab prevalence were confirmed. Elevated AAV9-Ab titers in children <6 weeks old decreased in all circumstances. Lower magnitudes of elevated titers declined more rapidly than greater magnitudes. Retesting was completed at the discretion of the treating clinician, so age at testing and time between tests varied. AAV9-Ab retesting should be considered when patients have elevated titers, and elevations at a young age are not a deterrent to eventual onasemnogene abeparvovec administration. Early disease-modifying treatment for SMA leads to optimal outcomes. Competing Interests: J.W.D. has received consulting fees from Novartis Gene Therapies, Inc., Biogen, Cytokinetics, Ionis Pharmaceuticals, Pfizer, Roche, and Sarepta Therapeutics; license fees or royalty payments from Athena Diagnostics; and research funding from Novartis Gene Therapies, Inc., Biogen, Cytokinetics, Roche, Sanofi Genzyme, and Sarepta Therapeutics. J.R.M. has received personal compensation for clinical trial consulting, serving on scientific advisory boards, and research support from Novartis Gene Therapies, Inc. A.H.M.B. is a consultant for Novartis Gene Therapies, Inc., and conducted research for Exicure, Inc. R.W.v.O. is an employee of Novartis Gene Therapies and owns Novartis stock or other equities. R.R.A. is an employee of Novartis Healthcare Private Limited, India. K.W.D. is an employee of Novartis Gene Therapies, Inc., and holds stock or other equities. (© 2023 The Author(s).)
Databáze:	MEDLINE
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