ArticlePloS one2010
Gene therapy in a humanized mouse model of familial hypercholesterolemia leads to marked regression of atherosclerosis.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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.
The trial behind it
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
43 citing papers in PubMed, 75 citations in OpenAlex.
- Review
- Review
- Applications and Research Advances in the Delivery of CRISPR/Cas9 Systems for the Treatment of Inherited Diseases.International journal of molecular sciences · 2023Review
- Review
- Gene therapy for liver diseases - progress and challenges.Nature reviews. Gastroenterology & hepatology · 2023Review
- Current Treatment Options in Homozygous Familial Hypercholesterolemia.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Novel Gene-Correction-Based Therapeutic Modalities for Monogenic Liver Disorders.Bioengineering (Basel, Switzerland) · 2022Review
- Advancements in the Treatment of Homozygous Familial Hypercholesterolemia.Journal of atherosclerosis and thrombosis · 2022Review
- The Functional Role of Lipoproteins in Atherosclerosis: Novel Directions for Diagnosis and Targeting Therapy.Aging and disease · 2022Review
- Genetically Engineered Hamster Models of Dyslipidemia and Atherosclerosis.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Developing a second-generation clinical candidate AAV vector for gene therapy of familial hypercholesterolemia.Molecular therapy. Methods & clinical development · 2021Article
- Management of Familial Hypercholesterolemia: Current Status and Future Perspectives.Journal of the Endocrine Society · 2021Review
- High-Density Lipoprotein-Targeted Therapies for Heart Failure.Biomedicines · 2020Review
- Macrophages in Atherosclerosis Regression.Arteriosclerosis, thrombosis, and vascular biology · 2020Review
- Article
- Bile-duct proliferation as an unexpected side-effect after AAV2-LDLR gene transfer to rabbit liver.Scientific reports · 2019Article
- Nuclease-Mediated Gene Therapies for Inherited Metabolic Diseases of the Liver.The Yale journal of biology and medicine · 2017Review
- Hepatic Tm6sf2 overexpression affects cellular ApoB-trafficking, plasma lipid levels, hepatic steatosis and atherosclerosis.Human molecular genetics · 2017Article
- Nonclinical Pharmacology/Toxicology Study of AAV8.TBG.mLDLR and AAV8.TBG.hLDLR in a Mouse Model of Homozygous Familial Hypercholesterolemia.Human gene therapy. Clinical development · 2017Article
- Non-Clinical Study Examining AAV8.TBG.hLDLR Vector-Associated Toxicity in Chow-Fed Wild-Type and LDLRHuman gene therapy. Clinical development · 2017Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundFamilial hypercholesterolemia (FH) is an autosomal codominant disorder caused by mutations in the low-density lipoprotein receptor (LDLR) gene. Homozygous FH patients (hoFH) have severe hypercholesterolemia leading to life threatening atherosclerosis in childhood and adolescence. Mice with germ line interruptions in the Ldlr and Apobec1 genes (Ldlr(-/-)Apobec1(-/-)) simulate metabolic and clinical aspects of hoFH, including atherogenesis on a chow diet. METHODS/PRINCIPAL
findingsIn this study, vectors based on adeno-associated virus 8 (AAV8) were used to deliver the gene for mouse Ldlr (mLDLR) to the livers of Ldlr(-/-)Apobec1(-/-) mice. A single intravenous injection of AAV8.mLDLR was found to significantly reduce plasma cholesterol and non-HDL cholesterol levels in chow-fed animals at doses as low as 3×10(9) genome copies/mouse. Whereas Ldlr(-/-)Apobec1(-/-) mice fed a western-type diet and injected with a control AAV8.null vector experienced a further 65% progression in atherosclerosis over 2 months compared with baseline mice, Ldlr(-/-)Apobec1(-/-) mice treated with AAV8.mLDLR realized an 87% regression of atherosclerotic lesions after 3 months compared to baseline mice. Immunohistochemical analyses revealed a substantial remodeling of atherosclerotic lesions. CONCLUSIONS/SIGNIFICANCE: Collectively, the results presented herein suggest that AAV8-based gene therapy for FH may be feasible and support further development of this approach. The pre-clinical data from these studies will enable for the effective translation of gene therapy into the clinic for treatment of FH.
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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.