ArticleMolecular therapy : the journal of the American Society of Gene Therapy2011
ATP7A gene addition to the choroid plexus results in long-term rescue of the lethal copper transport defect in a Menkes disease mouse model.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 77 citations in OpenAlex.
- Neurodevelopment and brain growth in classic Menkes disease is influenced by age and symptomatology at initiation of copper treatment.Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2014Trial
- Copper Nanoparticles Enable Multi-Compartment Cuproenzyme Metalation in Cellular Models of Copper Deficiency.ACS chemical biology · 2026Article
- Whole-brain biodistribution of AAV2, AAV8, and AAV-B10 after unilateral intracerebroventricular injection.Molecular therapy. Advances · 2026Article
- Disorders Mimicking Wilson's Disease: Clinical, Biochemical, and Molecular Perspectives for Accurate Differential Diagnosis.Diagnostics (Basel, Switzerland) · 2026Review
- Safety and efficacy of droxidopa for dysautonomia in adults with Menkes disease and occipital horn syndrome in the USA: a randomised phase 1/2a crossover trial.EClinicalMedicine · 2026Article
- Distinct signaling mechanisms and proteome phenotypes are elicited by compartment-specific genetic defects of copper homeostasis.bioRxiv : the preprint server for biology · 2026Article
- CRISPR prime editing as a promising therapeutic avenue for Menkes disease: the next step in correcting ATP7A mutations.Annals of medicine and surgery (2012) · 2026Article
- Intravenous AAV9-Science advances · 2025Article
- A primer on copper biology in the brain.Neurobiology of disease · 2025Review
- Choroid plexus-targeted viral gene therapy for alpha-mannosidosis, a prototypical neurometabolic lysosomal storage disease.Human molecular genetics · 2025Article
- Adaptive protein synthesis in genetic models of copper deficiency and childhood neurodegeneration.Molecular biology of the cell · 2025Article
- Restoration of Genetic Code in Macular Mouse Fibroblasts via APOBEC1-Mediated RNA Editing.Biomolecules · 2025Article
- Mammalian copper homeostasis: physiological roles and molecular mechanisms.Physiological reviews · 2025Review
- Adaptive protein synthesis in genetic models of copper deficiency and childhood neurodegeneration.bioRxiv : the preprint server for biology · 2024Article
- Widespread correction of brain pathology in feline alpha-mannosidosis by dose escalation of intracisternal AAV vector injection.Molecular therapy. Methods & clinical development · 2024Article
- Insights Into the Role of Copper in Neurodegenerative Diseases and the Therapeutic Potential of Natural Compounds.Current neuropharmacology · 2024Review
- Pigmentation and TYRP1 expression are mediated by zinc through the early secretory pathway-resident ZNT proteins.Communications biology · 2023Article
- Newly identified disorder of copper metabolism caused by variants in CTR1, a high-affinity copper transporter.Human molecular genetics · 2022Article
- Transduction characteristics of alternative adeno-associated virus serotypes in the cat brain by intracisternal delivery.Molecular therapy. Methods & clinical development · 2022Article
- Abnormal Development of Neural Stem Cell Niche in the Dentate Gyrus of Menkes Disease.International journal of stem cells · 2022Article
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
Abstract
Menkes disease is a lethal infantile neurodegenerative disorder of copper metabolism caused by mutations in a P-type ATPase, ATP7A. Currently available treatment (daily subcutaneous copper injections) is not entirely effective in the majority of affected individuals. The mottled-brindled (mo-br) mouse recapitulates the Menkes phenotype, including abnormal copper transport to the brain owing to mutation in the murine homolog, Atp7a, and dies by 14 days of age. We documented that mo-br mice on C57BL/6 background were not rescued by peripheral copper administration, and used this model to evaluate brain-directed therapies. Neonatal mo-br mice received lateral ventricle injections of either adeno-associated virus serotype 5 (AAV5) harboring a reduced-size human ATP7A (rsATP7A) complementary DNA (cDNA), copper chloride, or both. AAV5-rsATP7A showed selective transduction of choroid plexus epithelia and AAV5-rsATP7A plus copper combination treatment rescued mo-br mice; 86% survived to weaning (21 days), median survival increased to 43 days, 37% lived beyond 100 days, and 22% survived to the study end point (300 days). This synergistic treatment effect correlated with increased brain copper levels, enhanced activity of dopamine-β-hydroxylase, a copper-dependent enzyme, and correction of brain pathology. Our findings provide the first definitive evidence that gene therapy may have clinical utility in the treatment of Menkes disease.
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