ArticleThe AAPS journal2010
Phosphatidylinositol containing lipidic particles reduces immunogenicity and catabolism of factor VIII in hemophilia a mice.
Article in The AAPS journal, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Allometry of factor VIII and informed scaling of next-generation therapeutic proteins.Journal of pharmaceutical sciences · 2013Pooled it
- Article
- The Exploration of theFrontiers in microbiology · 2022Article
- An overview on the investigation of nanomaterials' effect on plasma components: immunoglobulins and coagulation factor VIII, 2010-2020 review.Nanoscale advances · 2021Review
- Lipidic Nanoparticles Comprising Phosphatidylinositol Mitigate Immunogenicity and Improve Efficacy of Recombinant Human Acid Alpha-Glucosidase in a Murine Model of Pompe Disease.Journal of pharmaceutical sciences · 2018Article
- Factor VIII associated with lipidic nanoparticles retains efficacy in the presence of anti-factor VIII antibodies in hemophilia A mice.Biopharmaceutics & drug disposition · 2016Article
- Soy Phosphatidylinositol-Containing Lipid Nanoparticle Prolongs the Plasma Survival and Hemostatic Efficacy of B-domain-Deleted Recombinant Canine Factor VIII in Hemophilia A Dogs.Journal of pharmaceutical sciences · 2016Article
- An RNAi therapeutic targeting antithrombin to rebalance the coagulation system and promote hemostasis in hemophilia.Nature medicine · 2015Article
- Soy phosphatidylinositol containing nanoparticle prolongs hemostatic activity of B-domain deleted factor VIII in hemophilia A mice.Journal of pharmaceutical sciences · 2015Article
- Effects of replacement of factor VIII amino acids Asp519 and Glu665 with Val on plasma survival and efficacy in vivo.The AAPS journal · 2014Article
- Nonlinear pharmacokinetics of factor VIII and its phosphatidylinositol lipidic complex in hemophilia A mice.Biopharmaceutics & drug disposition · 2014Article
- Native-like aggregates of factor VIII are immunogenic in von Willebrand factor deficient and hemophilia a mice.Journal of pharmaceutical sciences · 2012Article
- PEGylation of a factor VIII-phosphatidylinositol complex: pharmacokinetics and immunogenicity in hemophilia A mice.The AAPS journal · 2012Article
- Downregulation of CD40 signal and induction of TGF-β by phosphatidylinositol mediates reduction in immunogenicity against recombinant human Factor VIII.Journal of pharmaceutical sciences · 2012Article
- Phosphatidylinositol induces fluid phase formation and packing defects in phosphatidylcholine model membranes.Chemistry and physics of lipids · 2012Article
- A novel ovine ex vivo arteriovenous shunt model to test vascular implantability.Cells, tissues, organs · 2012Article
- Phospholipid binding lowers immunogenicity of human recombinant factor VIII in von Willebrand factor knockout mice.Thrombosis and haemostasis · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Factor VIII (FVIII) is an important cofactor in blood coagulation cascade. It is a multidomain protein that consists of six domains, NH2-A1-A2-B-A3-C1-C2-COOH. The deficiency or dysfunction of FVIII causes hemophilia A, a life-threatening bleeding disorder. Replacement therapy using recombinant FVIII (rFVIII) is the first line of therapy, but a major clinical complication is the development of inhibitory antibodies that abrogate the pharmacological activity of the administered protein. FVIII binds to anionic phospholipids (PL), such as phosphatidylinositol (PI), via lipid binding region within the C2 domain of FVIII. This lipid binding site not only consists of immunodominant epitopes but is also involved in von Willebrand factor binding that protects FVIII from degradation in vivo. Thus, we hypothesize that FVIII-PL complex will influence immunogenicity and catabolism of FVIII. The biophysical studies showed that PI binding did not alter conformation of the protein but improved intrinsic stability as measured by thermal denaturation studies. ELISA studies confirmed the involvement of the C2 domain in binding to PI containing lipid particles. PI binding prolonged the in vivo circulation time and reduced catabolism of FVIII in hemophilia A mice. FVIII-PI complex reduced inhibitor development in hemophilia A mice following intravenous and subcutaneous administration. The data suggest that PI binding reduces catabolism and immunogenicity of FVIII and has potential to be a useful therapeutic approach for hemophilia A.
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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.