ArticleNeurobiology of disease2015
Survival benefit and phenotypic improvement by hamartin gene therapy in a tuberous sclerosis mouse brain model.
Article in Neurobiology of disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- Article
- Tuberous sclerosis complex.Nature reviews. Disease primers · 2026Review
- Review
- Epilepsy and Cognitive Impairment in Childhood and Adolescence: A Mini-Review.Current neuropharmacology · 2023Review
- A Review of Targeted Therapies for Monogenic Epilepsy Syndromes.Frontiers in neurology · 2022Review
- Clinical Trial Design for Disease-Modifying Therapies for Genetic Epilepsies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Recent advances in gene therapy for neurodevelopmental disorders with epilepsy.Journal of neurochemistry · 2021Review
- Gene therapy for tuberous sclerosis complex type 2 in a mouse model by delivery of AAV9 encoding a condensed form of tuberin.Science advances · 2021Article
- Bone tissue and mineral metabolism in hereditary endocrine tumors: clinical manifestations and genetic bases.Orphanet journal of rare diseases · 2020Review
- Long-Term Therapeutic Efficacy of Intravenous AAV-Mediated Hamartin Replacement in Mouse Model of Tuberous Sclerosis Type 1.Molecular therapy. Methods & clinical development · 2019Article
- PI3K/mTOR Pathway Inhibition: Opportunities in Oncology and Rare Genetic Diseases.International journal of molecular sciences · 2019Review
- Autism spectrum disorder: prospects for treatment using gene therapy.Molecular autism · 2018Review
- Viral vectors for therapy of neurologic diseases.Neuropharmacology · 2017Review
- Molecular rescue of Tsc1-ablated cortical tuber mice.Oncotarget · 2017Article
- FMRP Expression Levels in Mouse Central Nervous System Neurons Determine Behavioral Phenotype.Human gene therapy · 2016Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
We examined the potential benefit of gene therapy in a mouse model of tuberous sclerosis complex (TSC) in which there is embryonic loss of Tsc1 (hamartin) in brain neurons. An adeno-associated virus (AAV) vector (serotype rh8) expressing a tagged form of hamartin was injected into the cerebral ventricles of newborn pups with the genotype Tsc1(cc) (homozygous for a conditional floxed Tsc1 allele) SynI-cre(+), in which Tsc1 is lost selectively in neurons starting at embryonic day 12. Vector-treated Tsc1(cc)SynIcre(+) mice showed a marked improvement in survival from a mean of 22 days in non-injected mice to 52 days in AAV hamartin vector-injected mice, with improved weight gain and motor behavior in the latter. Pathologic studies showed normalization of neuron size and a decrease in markers of mTOR activation in treated as compared to untreated mutant littermates. Hence, we show that gene replacement in the brain is an effective therapeutic approach in this mouse model of TSC1. Our strategy for gene therapy has the advantages that therapy can be achieved from a single application, as compared to repeated treatment with drugs, and that AAV vectors have been found to have minimal to no toxicity in clinical trials for other neurologic conditions. Although there are many additional issues to be addressed, our studies support gene therapy as a useful approach in TSC patients.
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