Trial reportGene therapy2016
Prevalence of AAV1 neutralizing antibodies and consequences for a clinical trial of gene transfer for advanced heart failure.
Trial report in Gene therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01643330 (A Phase 2b, Double-Blind, Placebo-Controlled, Multinational, Multicenter, Randomized Study Evaluating the Safety and Efficacy of Intracoronary Administration of MYDICAR®), which is not on this map. Cited by 71 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
A Phase 2b, Double-Blind, Placebo-Controlled, Multinational, Multicenter, Randomized Study Evaluating the Safety and Efficacy of Intracoronary Administration of MYDICAR® (AAV1/SERCA2a) in Subjects With Heart Failure
Who cites it
71 citing papers in PubMed, 105 citations in OpenAlex.
- Bilateral gene therapy in children with autosomal recessive deafness 9: single-arm trial results.Nature medicine · 2024Trial
- Environmental and developmental factors shape anti-AAV immunity in pigs.Gene therapy · 2026Article
- Vasculogenic tissue nanotransfection accelerates functional recovery after peripheral nerve injury.Science advances · 2026Article
- Seroprevalence of anti-AAV antibodies in a healthy adult Spanish population: findings from the SAAVIA study.Gene therapy · 2026Article
- Gene Therapy for Heart Failure.Journal of cardiovascular translational research · 2026Review
- Gene Therapy for Heart Failure: Impact on Mitochondrial Dysfunction.Biomedicines · 2026Review
- Global seroprevalence of neutralizing and total antibodies against AAV vectors and their impact on the clinical gene therapy landscape: a scoping review.Frontiers in medicine · 2026Review
- Evaluation of Lipid Nanoparticles as Vehicles for Optogenetic Delivery in Primary Cortical Neurons.Pharmaceutics · 2025Article
- Pre-Existing Anti-Adeno-Associated Virus Immunity in Gene Therapy: Mechanisms, Challenges, and Potential Solutions.Human gene therapy · 2025Review
- Gene therapy in cardiac and vascular diseases: a review of approaches to treat genetic and common cardiovascular diseases with novel gene-based therapeutics.Cardiovascular research · 2025Review
- AAV microdystrophin gene replacement therapy for Duchenne muscular dystrophy: progress and prospects.Gene therapy · 2025Review
- SAR-Guided Development of Small-Molecule SERCA2a Activators: Discovery of Potent Indoline, Benzofuran, and Benzodioxole Analogs for Cardiovascular Applications.Journal of medicinal chemistry · 2025Article
- Neutralizing Antibodies: Role in Immune Response and Viral Vector Based Gene Therapy.International journal of molecular sciences · 2025Review
- Pre-existing Anti-AAV9 antibodies in the Chinese healthy and rare disease populations: Implications for gene therapy.Virus research · 2025Article
- Review
- Global seroprevalence of neutralizing antibodies against adeno-associated virus serotypes used for human gene therapies.Molecular therapy. Methods & clinical development · 2024Article
- Multicenter assessment and longitudinal study of the prevalence of antibodies and related adaptive immune responses to AAV in adult males with hemophilia.Gene therapy · 2024Article
- Understanding AAV vector immunogenicity: from particle to patient.Theranostics · 2024Review
- Gene therapy for the heart: encapsulated viruses to the rescue.Extracellular vesicles and circulating nucleic acids · 2024Article
- Extracellular Vesicle-Encapsulated Adeno-Associated Viruses for Therapeutic Gene Delivery to the Heart.Circulation · 2023Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 7 institutions in 3 countries.
Funding
Abstract
Adeno-associated virus serotype 1 (AAV1) has many advantages as a gene therapy vector, but the presence of pre-existing neutralizing antibodies (NAbs) is an important limitation. This study was designed to determine: (1) characteristics of AAV NAbs in human subjects, (2) prevalence of AAV1 NAbs in heart failure patients and (3) utility of aggressive immunosuppressive therapy in reducing NAb seroconversion in an animal model. NAb titers were assessed in a cohort of heart failure patients and in patients screened for a clinical trial of gene therapy with AAV1 carrying the sarcoplasmic reticulum calcium ATPase gene (AAV1/SERCA2a). AAV1 NAbs were found in 59.5% of 1552 heart failure patients. NAb prevalence increased with age (P=0.001) and varied geographically. The pattern of NAb titers suggested that exposure is against AAV2, with AAV1 NAb seropositivity due to crossreactivity. The effects of immunosuppression on NAb formation were tested in mini-pigs treated with immunosuppressant therapy before, during and after a single AAV1/SERCA2a infusion. Aggressive immunosuppression did not prevent formation of AAV1 NAbs. We conclude that immunosuppression is unlikely to be a viable solution for repeat AAV1 dosing. Strategies to reduce NAbs in heart failure patients are needed to increase eligibility for gene transfer using AAV vectors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.