ArticleMolecular therapy. Methods & clinical development2018
Toxicology Study of Intra-Cisterna Magna Adeno-Associated Virus 9 Expressing Human Alpha-L-Iduronidase 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 73 papers.
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Who cites it
73 citing papers in PubMed, 103 citations in OpenAlex.
- Optimization of AAV tools to target Müller glial cells for retinal gene therapy.Molecular therapy. Advances · 2026Article
- Intra-CNS AAV9-Molecular therapy. Advances · 2026Article
- Next generation AAV-F capsid gene therapy rescues disease pathology in a model of pyruvate dehydrogenase complex deficiency.Molecular therapy. Advances · 2026Article
- Challenging the more-is-better dogma: A precision-optimized AAV gene therapy for SMA.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Repeated Intra-cisterna Magna Injections with Amyloid-beta Oligomers to Induce Alzheimer's Disease in Cynomolgus Monkey (Experimental neurobiology · 2026Article
- Adeno-associated virus-induced neurotoxicity is prevented by CpG depletion.Molecular therapy. Advances · 2026Article
- Review
- 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
- rAAV9 vector biodistribution in nonhuman primate brain and spinal cord following lumbar intrathecal infusion.Frontiers in medicine · 2026Article
- 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
- AAV9-mediated KCC2 upregulation enhances functional recovery following cervical spinal cord injury.Communications biology · 2025Article
- Transabdominal ultrasound guided AAV9-GFP delivery in fetal pigs: a translational and minimally invasive model for in utero fetal gene therapy.Gene therapy · 2025Article
- Preclinical evaluation of AAV9-coSMN1 gene therapy for spinal muscular atrophy: efficacy and safety in mouse models and non-human primates.Molecular medicine (Cambridge, Mass.) · 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
- Intrathecal or intravenous AAV9-IDUA/RGX-111 at minimal effective dose prevents cardiac, skeletal and neurologic manifestations of murine MPS I.Molecular therapy. Methods & clinical development · 2024Article
- Comparative assessment of the transduction efficiency and safety associated with the delivery of AAV9-GFP vector via lumbar puncture to cynomolgus macaques with and without anti-AAV9 pre-existing antibodies.Molecular therapy. Methods & clinical development · 2024Article
- 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
13 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mucopolysaccharidosis type I is a recessive genetic disease caused by deficiency of the lysosomal enzyme α-L-iduronidase, which leads to a neurodegenerative and systemic disease called Hurler syndrome in its most severe form. Several clinical trials are evaluating adeno-associated virus serotype 9 (AAV9) for the treatment of neurodegenerative diseases. Although these trials focus on systemic or lumbar administration, intrathecal administration via suboccipital puncture into the cisterna magna has demonstrated remarkable efficacy in large animals. We, therefore, conducted a good laboratory practice-compliant non-clinical study to investigate the safety of suboccipital AAV9 gene transfer of human α-L-iduronidase into nonhuman primates. We dosed 22 rhesus macaques, including three immunosuppressed animals, with vehicle or one of two doses of vector. We assessed in-life safety and immune responses. Animals were euthanized 14, 90, or 180 days post-vector administration and evaluated for histopathology and biodistribution. No procedure-related lesions or adverse events occurred. All vector-treated animals showed a dose-dependent mononuclear pleocytosis in the cerebrospinal fluid and minimal to moderate asymptomatic degeneration of dorsal root ganglia neurons and associated axons. These studies support the clinical development of suboccipital AAV delivery for Hurler syndrome and highlight a potential sensory neuron toxicity that warrants careful monitoring in first-in-human studies.
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