ArticleThe Journal of clinical investigation2008
Long-term expression of murine activated factor VII is safe, but elevated levels cause premature mortality.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Protein-Engineered Coagulation Factors for Hemophilia Gene Therapy.Molecular therapy. Methods & clinical development · 2019Review
- Gene-based FVIIa prophylaxis modulates the spontaneous bleeding phenotype of hemophilia A rats.Blood advances · 2019Article
- Factor X Friuli Coagulation Disorder: Almost 50 Years Later.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis · 2018Review
- Gene Delivery of Activated Factor VII Using Alternative Adeno-Associated Virus Serotype Improves Hemostasis in Hemophiliac Mice with FVIII Inhibitors and Adeno-Associated Virus Neutralizing Antibodies.Human gene therapy · 2017Article
- Targeting factor VIII expression to platelets for hemophilia A gene therapy does not induce an apparent thrombotic risk in mice.Journal of thrombosis and haemostasis : JTH · 2017Article
- Employing a gain-of-function factor IX variant R338L to advance the efficacy and safety of hemophilia B human gene therapy: preclinical evaluation supporting an ongoing adeno-associated virus clinical trial.Human gene therapy · 2015Article
- The endothelial protein C receptor enhances hemostasis of FVIIa administration in hemophilic mice in vivo.Blood · 2014Article
- Lessons Learned from Animal Models of Inherited Bleeding Disorders.Hematology education. European Hematology Association. Congress. Education Program · 2014Article
- Article
- Animal models of hemophilia.Progress in molecular biology and translational science · 2012Review
- Engineering Factor Viii for Hemophilia Gene Therapy.Journal of genetic syndromes & gene therapy · 2011Article
- Pharmacokinetics, pharmacodynamics and safety of recombinant canine FVIIa in a study dosing one haemophilia A and one haemostatically normal dog.Haemophilia : the official journal of the World Federation of Hemophilia · 2011Article
- A zymogen-like factor Xa variant corrects the coagulation defect in hemophilia.Nature biotechnology · 2011Article
- Article
- Long-term expression of canine FVIIa in hemophilic dogs.Thrombosis research · 2010Review
- Animal models of FVIIa gene expression: their role in the future development of haemophilia treatment.Haemophilia : the official journal of the World Federation of Hemophilia · 2010Article
- Nanocapsule-delivered Sleeping Beauty mediates therapeutic Factor VIII expression in liver sinusoidal endothelial cells of hemophilia A mice.The Journal of clinical investigation · 2009Article
- The role of tissue factor and factor VIIa in hemostasis.Anesthesia and analgesia · 2009Review
- Article
- Mouse models of cystathionine beta-synthase deficiency reveal significant threshold effects of hyperhomocysteinemia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Intravenous infusion of recombinant human activated Factor VII (FVIIa) has been used for over a decade in the successful management of bleeding episodes in patients with inhibitory antibodies to Factor VIII or Factor IX. Previously, we showed that expression of murine FVIIa (mFVIIa) from an adeno-associated viral (AAV) vector corrected abnormal hemostatic parameters in hemophilia B mice. To pursue this as a therapeutic approach, we sought to define safe and effective levels of FVIIa for continuous expression. In mice transgenic for mFVIIa or injected with AAV-mFVIIa, we analyzed survival, expression levels, in vitro and in vivo coagulation tests, and histopathology for up to 16 months after birth/mFVIIa expression. We found that continuous expression of mFVIIa at levels at or below 1.5 microg/ml was safe, effective, and compatible with a normal lifespan. However, expression levels of 2 microg/ml or higher were associated with thrombosis and early mortality, with pathologic findings in the heart and lungs that were rescued in a low-factor X (low-FX) mouse background, suggesting a FX-mediated effect. The findings from these mouse models of continuous FVIIa expression have implications for the development of a safe gene transfer approach for hemophilia and are consistent with the possibility of thromboembolic risk of continuously elevated FVIIa levels.
Indexed as
Identifiers
What OpenQuestion holds
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.