ArticleMolecular therapy. Methods & clinical development2018
Toxicology Study of Intra-Cisterna Magna Adeno-Associated Virus 9 Expressing Iduronate-2-Sulfatase in Rhesus Macaques.
Article in Molecular therapy. Methods & clinical development, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 83 citations in OpenAlex.
- Intra-CNS AAV9-Molecular therapy. Advances · 2026Article
- The dose makes the poison: Mechanisms of cytotoxicity of high-dose AAV vectors.Molecular therapy. Advances · 2026Article
- Adeno-associated virus-induced neurotoxicity is prevented by CpG depletion.Molecular therapy. Advances · 2026Article
- Article
- Immune Toxicities in AAV Gene Therapy: Overview for Clinicians.International journal of molecular sciences · 2026Review
- Deciphering the role and contribution of AAV immune responses to DRG toxicity.Molecular therapy. Advances · 2026Article
- Non-clinical safety considerations on genome editing using the CRISPR/Cas system.Genes & diseases · 2026Review
- Inhibition of immune response reduces pathology in dorsal root ganglia and peripheral nerves in cynomolgus macaques following AAV gene therapy.Molecular therapy. Methods & clinical development · 2025Article
- Biodistribution of AAV1, AAV5, AAV9, and AAVDJ serotypes after intra-cisterna magna delivery in non-human primates.Molecular therapy. Methods & clinical development · 2025Article
- A dose escalation and safety study of AAVrh10-mediated Schwann cell-targeted gene therapy for CMT1X.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Adeno-associated virus vectors and neurotoxicity-lessons from preclinical and human studies.Gene therapy · 2025Review
- Next-generation strategies to improve safety and efficacy of adeno-associated virus-based gene therapy for hemophilia: lessons from clinical trials in other gene therapies.Haematologica · 2024Review
- Pre-clinical development of AP4B1 gene replacement therapy for hereditary spastic paraplegia type 47.EMBO molecular medicine · 2024Article
- A minimally invasive endovascular approach to the cerebellopontine angle cistern enables broad CNS biodistribution of scAAV9-CB-GFP.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- The potential of gene delivery for the treatment of traumatic brain injury.Journal of neuroinflammation · 2024Review
- Prenatal AAV9-GFP administration in fetal lambs results in transduction of female germ cells and maternal exposure to virus.Molecular therapy. Methods & clinical development · 2024Article
- A shedding analysis after AAV8 CNS injection revealed fragmented viral DNA without evidence of functional AAV particles in mice.Gene therapy · 2024Article
- Adeno-associated virus as a delivery vector for gene therapy of human diseases.Signal transduction and targeted therapy · 2024Review
- AAV8 vector induced gliosis following neuronal transgene expression.Frontiers in neuroscience · 2024Article
- Viral Vector-Based Gene Therapy for Epilepsy: What Does the Future Hold?Molecular diagnosis & therapy · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hunter syndrome is an X-linked recessive disease caused by deficiency of the lysosomal enzyme iduronate-2-sulfatase. The severe form of this progressive, systemic, and neurodegenerative disease results in loss of cognitive skills and early death. Several clinical trials are evaluating adeno-associated virus 9 for the treatment of neurodegenerative diseases using systemic or intrathecal lumbar administration. In large animals, administration via suboccipital puncture gives better brain transduction than lumbar administration. Here, we conducted a good laboratory practice-compliant investigational new drug-enabling study to determine the safety of suboccipital adeno-associated virus 9 gene transfer of human iduronate-2-sulfatase into nonhuman primates. Thirteen rhesus macaques received vehicle or one of two doses of vector with or without immunosuppression. We assessed in-life safety and immune responses. Animals were euthanized 90 days post-administration and sampled for histopathology and biodistribution. The procedure was well tolerated in all animals. Minimal mononuclear cerebrospinal fluid pleocytosis occurred in some animals. Asymptomatic minimal-to-moderate toxicity to some dorsal root ganglia sensory neurons and their associated axons occurred in all vector-treated animals. This study supports the clinical development of suboccipital adeno-associated virus 9 delivery for severe Hunter syndrome and highlights a potential toxicity that warrants monitoring in first-in-human studies.
Indexed as
Identifiers
What OpenQuestion holds
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.