ArticleHuman gene therapy2017
Intranasal Adeno-Associated Virus Mediated Gene Delivery and Expression of Human Iduronidase in the Central Nervous System: A Noninvasive and Effective Approach for Prevention of Neurologic Disease in Mucopolysaccharidosis Type I.
Article in Human gene therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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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.
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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
38 citing papers in PubMed, 65 citations in OpenAlex.
- Intranasal versus intravenous AAV delivery: A comparative analysis of brain-targeting efficiency and peripheral exposure in mice.Gene therapy · 2026Article
- A Comprehensive Update on Pompe Disease: From Existing Therapies to Emerging Curative Strategies.International journal of molecular sciences · 2026Review
- Recent Advances in Nose-to-Brain Gene Delivery for Central Nervous System Disorders.Pharmaceutics · 2025Review
- Advances and Challenges in Adeno-Associated Virus Gene Therapy Applications of Localized Delivery Strategies.Current medical science · 2025Review
- Intranasal insulin for the treatment of alcohol use disorder: design and methodology of an alcohol interaction randomized controlled trial.Contemporary clinical trials communications · 2025Article
- Intranasal Drug Delivery Technology in the Treatment of Central Nervous System Diseases: Challenges, Advances, and Future Research Directions.Pharmaceutics · 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
- Engineering memory T cells as a platform for long-term enzyme replacement therapy in lysosomal storage disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Adeno-associated virus vector delivery to the brain: Technology advancements and clinical applications.Advanced drug delivery reviews · 2024Review
- The potential of gene delivery for the treatment of traumatic brain injury.Journal of neuroinflammation · 2024Review
- Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.Biomedicines · 2024Review
- Neurologic Recovery in MPS I and MPS II Mice by AAV9-Mediated Gene Transfer to the CNS After the Development of Cognitive Dysfunction.Human gene therapy · 2023Article
- Mucopolysaccharidoses and the blood-brain barrier.Fluids and barriers of the CNS · 2022Review
- Targeting the lung epithelium after intravenous delivery by directed evolution of underexplored sites on the AAV capsid.Molecular therapy. Methods & clinical development · 2022Article
- Using the Intranasal Route to Administer Drugs to Treat Neurological and Psychiatric Illnesses: Rationale, Successes, and Future Needs.CNS drugs · 2022Review
- Liver-directed gene therapy corrects neurologic disease in a murine model of mucopolysaccharidosis type I-Hurler.Molecular therapy. Methods & clinical development · 2022Article
- Experimental approaches for manipulating choroid plexus epithelial cells.Fluids and barriers of the CNS · 2022Review
- Customized blood-brain barrier shuttle peptide to increase AAV9 vector crossing the BBB and augment transduction in the brain.Biomaterials · 2022Article
- Non-Viral Delivery of RNA Gene Therapy to the Central Nervous System.Pharmaceutics · 2022Review
- Routes of administration for adeno-associated viruses carrying gene therapies for brain diseases.Frontiers in molecular neuroscience · 2022Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mucopolysaccharidosis type I (MPS I) is a progressive, multi-systemic, inherited metabolic disease caused by deficiency of α-L-iduronidase (IDUA). Current treatments for this disease are ineffective in treating central nervous system (CNS) disease due to the inability of lysosomal enzymes to traverse the blood-brain barrier. A noninvasive and effective approach was taken in the treatment of CNS disease by intranasal administration of an IDUA-encoding adeno-associated virus serotype 9 (AAV9) vector. Adult IDUA-deficient mice aged 3 months were instilled intranasally with AAV9-IDUA vector. Animals sacrificed 5 months post instillation exhibited IDUA enzyme activity levels that were up to 50-fold that of wild-type mice in the olfactory bulb, with wild-type levels of enzyme restored in all other parts of the brain. Intranasal treatment with AAV9-IDUA also resulted in the reduction of tissue glycosaminoglycan storage materials in the brain. There was strong IDUA immunofluorescence staining of tissue sections observed in the nasal epithelium and olfactory bulb, but there was no evidence of the presence of transduced cells in other portions of the brain. This indicates that reduction of storage materials most likely occurred as a result of enzyme diffusion from the olfactory bulb and the nasal epithelium into deeper areas of the brain. At 8 months of age, neurocognitive testing using the Barnes maze to assess spatial navigation demonstrated that treated IDUA-deficient mice were no different from normal control animals, while untreated IDUA-deficient mice exhibited significant learning and navigation deficits. This novel, noninvasive strategy for intranasal AAV9-IDUA instillation could potentially be used to treat CNS manifestations of human MPS I.
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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.