ArticleProceedings of the National Academy of Sciences of the United States of America2014
Liver-directed gene therapy corrects cardiovascular lesions in feline mucopolysaccharidosis type I.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 47 citations in OpenAlex.
- Age-sensitive response of systemic AAV-mediated gene therapy in a newly characterized feline model of mucolipidosis II.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- 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
- Lentiviral Gene Therapy for Mucopolysaccharidosis II with Tagged Iduronate 2-Sulfatase Prevents Life-Threatening Pathology in Peripheral Tissues But Fails to Correct Cartilage.Human gene therapy · 2024Article
- In vivo adenine base editing corrects newborn murine model of Hurler syndrome.Molecular biomedicine · 2023Article
- 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
- First-in-human in vivo genome editing via AAV-zinc-finger nucleases for mucopolysaccharidosis I/II and hemophilia B.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Liver-directed gene therapy corrects neurologic disease in a murine model of mucopolysaccharidosis type I-Hurler.Molecular therapy. Methods & clinical development · 2022Article
- Pre-operative Considerations in Adult Mucopolysaccharidosis Patients Planned for Cardiac Intervention.Frontiers in cardiovascular medicine · 2022Review
- Non-cardiac Manifestations in Adult Patients With Mucopolysaccharidosis.Frontiers in cardiovascular medicine · 2022Review
- A novel therapeutic strategy for skeletal disorders: Proof of concept of gene therapy for X-linked hypophosphatemia.Science advances · 2021Article
- Oxidative Stress in Mucopolysaccharidoses: Pharmacological Implications.Molecules (Basel, Switzerland) · 2021Review
- Mucopolysaccharidoses type I gene therapy.Journal of inherited metabolic disease · 2021Review
- Gene Therapy for Lysosomal Storage Disorders: Ongoing Studies and Clinical Development.Biomolecules · 2021Review
- Mucopolysaccharidosis Type I: Current Treatments, Limitations, and Prospects for Improvement.Biomolecules · 2021Review
- Comparative Effectiveness of Intracerebroventricular, Intrathecal, and Intranasal Routes of AAV9 Vector Administration for Genetic Therapy of Neurologic Disease in Murine Mucopolysaccharidosis Type I.Frontiers in molecular neuroscience · 2021Article
- Intravenous delivery for treatment of mucopolysaccharidosis type I: A comparison of AAV serotypes 9 and rh10.Molecular genetics and metabolism reports · 2020Article
- Mucopolysaccharidoses I and II: Brief Review of Therapeutic Options and Supportive/Palliative Therapies.BioMed research international · 2020Review
- Effects of gene therapy on cardiovascular symptoms of lysosomal storage diseases.Genetics and molecular biology · 2019Article
- Gene therapy for mucopolysaccharidoses: in vivo and ex vivo approaches.Italian journal of pediatrics · 2018Review
- Canine and Feline Models of Human Genetic Diseases and Their Contributions to Advancing Clinical Therapies .The Yale journal of biology and medicine · 2017Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
Abstract
Patients with mucopolysaccharidosis type I (MPS I), a genetic deficiency of the lysosomal enzyme α-l-iduronidase (IDUA), exhibit accumulation of glycosaminoglycans in tissues, with resulting diverse clinical manifestations including neurological, ocular, skeletal, and cardiac disease. MPS I is currently treated with hematopoietic stem cell transplantation or weekly enzyme infusions, but these therapies have significant drawbacks for patient safety and quality of life and do not effectively address some of the most critical clinical sequelae, such as life-threatening cardiac valve involvement. Using the naturally occurring feline model of MPS I, we tested liver-directed gene therapy as a means of achieving long-term systemic IDUA reconstitution. We treated four MPS I cats at 3-5 mo of age with an adeno-associated virus serotype 8 vector expressing feline IDUA from a liver-specific promoter. We observed sustained serum enzyme activity for 6 mo at ∼ 30% of normal levels in one animal, and in excess of normal levels in three animals. Remarkably, treated animals not only demonstrated reductions in glycosaminoglycan storage in most tissues, but most also exhibited complete resolution of aortic valve lesions, an effect that has not been previously observed in this animal model or in MPS I patients treated with current therapies. These data point to clinically meaningful benefits of the robust enzyme expression achieved with hepatic gene transfer that extend beyond the economic and quality of life advantages over lifelong enzyme infusions.
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Registered trials
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