ArticleProceedings of the National Academy of Sciences of the United States of America2011
Platelet gene therapy improves hemostatic function for integrin alphaIIbbeta3-deficient dogs.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 57 citations in OpenAlex.
- Generation of Novel Monoclonal Antibodies Recognizing Rabbit CD34 Antigen.Biomolecules · 2025Article
- A single F153Sβ3 mutation causes constitutive integrin αIIbβ3 activation in a variant form of Glanzmann thrombasthenia.Blood advances · 2023Article
- Inherited Platelet Disorders: An Updated Overview.International journal of molecular sciences · 2021Review
- Gene Therapy for Inherited Bleeding Disorders.Seminars in thrombosis and hemostasis · 2021Review
- Profiling the Genetic and Molecular Characteristics of Glanzmann Thrombasthenia: Can It Guide Current and Future Therapies?Journal of blood medicine · 2021Review
- Glanzmann Thrombasthenia: Perspectives from Clinical Practice on Accurate Diagnosis and Optimal Treatment Strategies.Journal of blood medicine · 2021Review
- [The progresses in research and treatment of inherited platelet disorders].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2018Article
- [Current state and prospect in treatment of Glanzmann' s thrombasthenia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2016Article
- Genetic engineering of platelets to neutralize circulating tumor cells.Journal of controlled release : official journal of the Controlled Release Society · 2016Article
- Review
- A novel canine model of immune thrombocytopenia: has immune thrombocytopenia (ITP) gone to the dogs?British journal of haematology · 2014Article
- In vivo enrichment of genetically manipulated platelets corrects the murine hemophilic phenotype and induces immune tolerance even using a low multiplicity of infection.Journal of thrombosis and haemostasis : JTH · 2014Article
- Article
- Glanzmann thrombasthenia: state of the art and future directions.Seminars in thrombosis and hemostasis · 2013Review
- C560Rβ3 caused platelet integrin αII b β3 to bind fibrinogen continuously, but resulted in a severe bleeding syndrome and increased murine mortality.Journal of thrombosis and haemostasis : JTH · 2013Article
- Hematopoietic stem cell gene therapy:assessing the relevance of preclinical models.Seminars in hematology · 2013Review
- Platelet-targeted gene therapy with human factor VIII establishes haemostasis in dogs with haemophilia A.Nature communications · 2013Article
- Engineered Hematopoietic Stem Cells as Therapeutics for Hemophilia A.Journal of genetic syndromes & gene therapy · 2011Article
- A novel ITGA2B double cytosine frameshift variant (c.1986_1987insCC) leads to Glanzmann's thrombasthenia in a cat.Journal of veterinary internal medicineArticle
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Activated blood platelets mediate the primary response to vascular injury. Although molecular abnormalities of platelet proteins occur infrequently, taken collectively, an inherited platelet defect accounts for a bleeding diathesis in ≈1:20,000 individuals. One rare example of a platelet disorder, Glanzmann thrombasthenia (GT), is characterized by life-long morbidity and mortality due to molecular abnormalities in a major platelet adhesion receptor, integrin αIIbβ3. Transfusion therapy is frequently inadequate because patients often generate antibodies to αIIbβ3, leading to immune-mediated destruction of healthy platelets. In the most severe cases allogeneic bone marrow transplantation has been used, yet because of the risk of the procedure it has been limited to few patients. Thus, hematopoietic stem cell gene transfer was explored as a strategy to improve platelet function within a canine model for GT. Bleeding complications necessitated the use of a mild pretransplant conditioning regimen; therefore, in vivo drug selection was used to improve engraftment of autologously transplanted cells. Approximately 5,000 αIIbβ3 receptors formed on 10% of platelets. These modest levels allowed platelets to adhere to αIIbβ3's major ligand (fibrinogen), form aggregates, and mediate retraction of a fibrin clot. Remarkably, improved hemostatic function was evident, with ≤135-fold reduced blood loss, and improved buccal bleeding times decreased to 4 min for up to 5 y after transplant. One of four transplanted dogs developed a significant antibody response to αIIbβ3 that was attenuated effectively with transient immune suppression. These results indicate that gene therapy could become a practical approach for treating inherited platelet defects.
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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.