ArticleNeurology2025
Reduction of Preexisting AAV9 Antibody Titers Before Onasemnogene Abeparvovec Administration in Twins With Spinal Muscular Atrophy.
Article in Neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
4 citing papers in PubMed.
- VTX-PID as a novel recombinant immunoglobulin G-degrading enzyme (IdeS) for efficient AAV-based gene therapy in participants with neutralizing antibodies: results of the phase I first-in-human NAVIgATE study.Frontiers in immunology · 2026Trial
- Meeting report: 2025 muscular dystrophy association summit on 'safety and challenges in gene therapy of neuromuscular diseases'.Journal of neuromuscular diseases · 2026Article
- Gene replacement therapy for Piga GPI-anchor deficiency in the developing nervous system.bioRxiv : the preprint server for biology · 2025Article
- Impact of pre-existing immunity on safety and biodistribution of a single AAV9 vector intrathecal injection in cynomolgus monkeys.Molecular therapy. Methods & clinical development · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
objectivesPreexisting immunity to adeno-associated viruses (AAVs) presents a major obstacle to eligibility for gene therapy.
methodsWe determined the feasibility of immunodepletion with therapeutic plasma exchange and rituximab to lower anti-AAV9 antibody (AAV Ab) titers before gene therapy for spinal muscular atrophy (SMA).
resultsTwin 21-month-old brothers with SMA presented with AAV9 Ab titers of 1:800, exceeding the limit of 1:50 for eligibility to receive onasemnogene abeparvovec (OA). Because there was a low expectation of spontaneous reduction in Ab titers, they received 11 plasma exchanges and 2 doses of rituximab, leading to their AAV9 Ab titers dropping to the eligibility range for OA. During their OA infusions, despite methylprednisolone pretreatment, both twins experienced acute hypersensitivity reactions characterized by urticaria, wheezing, and GI disturbances that resolved with epinephrine. The limited dose of OA they received did not lead to marked clinical improvement. DISCUSSION: Therapeutic plasma exchange and rituximab successfully reduced the AAV Ab titers to the range of eligibility, but this regimen combined with corticosteroids was not sufficient to prevent infusion reactions to AAV gene therapy in our patients with preexisting AAV Abs. Further studies are needed to define a protocol that could enable patients to receive AAV-based gene therapy in the presence of preexisting immunity.
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