scholarly journals Novel therapeutic approach for hemophilia using gene delivery of an engineered secreted activated Factor VII

2004 ◽  
Vol 113 (7) ◽  
pp. 1025-1031 ◽  
Author(s):  
Paris Margaritis ◽  
Valder R. Arruda ◽  
Majed Aljamali ◽  
Rodney M. Camire ◽  
Alexander Schlachterman ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Therapeutic Approach ◽  
Factor Vii ◽  
Activated Factor Vii ◽  
Novel Therapeutic

scholarly journals Reducing Amyloid Plaque Burden via Ex Vivo Gene Delivery of an Aβ-Degrading Protease: A Novel Therapeutic Approach to Alzheimer Disease

PLoS Medicine ◽  
2007 ◽  
Vol 4 (8) ◽  
pp. e262 ◽  
Author(s):  
Matthew L Hemming ◽  
Michaela Patterson ◽  
Casper Reske-Nielsen ◽  
Ling Lin ◽  
Ole Isacson ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Alzheimer Disease ◽  
Therapeutic Approach ◽  
Ex Vivo ◽  
Amyloid Plaque ◽  
Plaque Burden ◽  
Novel Therapeutic

scholarly journals Catalytic domain modification and viral gene delivery of activated factor VII confers hemostasis at reduced expression levels and vector doses in vivo

Blood ◽  
2011 ◽  
Vol 117 (15) ◽  
pp. 3974-3982 ◽  
Author(s):  
Paris Margaritis ◽  
Elise Roy ◽  
Armida Faella ◽  
Harre D. Downey ◽  
Lacramioara Ivanciu ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Catalytic Domain ◽  
Factor Ix ◽  
Factor Vii ◽  
Viral Gene ◽  
Expression Levels ◽  
Activated Factor Vii ◽  
Coagulant Activity

Abstract Catalytic domain variants of activated factor VII (FVIIa) with enhanced hemostatic properties are highly attractive for the treatment of bleeding disorders via gene-based therapy. To explore this in a hemophilic mouse model, we characterized 2 variants of murine activated FVII (mFVIIa-VEAY and mFVIIa-DVQ) with modified catalytic domains, based on recombinant human FVIIa (rhFVIIa) variants. Using purified recombinant proteins, we showed that murine FVIIa (mFVIIa) and variants had comparable binding to human and murine tissue factor (TF) and exhibited similar extrinsic coagulant activity. In vitro in the absence of TF, the variants showed a 6- to 17-fold enhanced proteolytic and coagulant activity relative to mFVIIa, but increased inactivation by antithrombin. Gene delivery of mFVIIa-VEAY resulted in long-term, effective hemostasis at 5-fold lower expression levels relative to mFVIIa in hemophilia A mice or in hemophilia B mice with inhibitors to factor IX. However, expression of mFVIIa-VEAY at 14-fold higher than therapeutic levels resulted in a progressive mortality to 70% within 6 weeks after gene delivery. These results are the first demonstration of the hemostatic efficacy of continuous expression, in the presence or absence of inhibitors, of a high-activity gene-based FVIIa variant in an animal model of hemophilia.

Very Low Activated Factor VII and Reduced Factor VII Antigen in Familial Abetalipoproteinaemia

1998 ◽  
Vol 80 (08) ◽  
pp. 233-238 ◽  
Author(s):  
K. A. Mitropoulos ◽  
M. N. Nanjee ◽  
D. J. Howarth ◽  
J. C. Martin ◽  
M. P. Esnouf ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Positive Association ◽  
Factor Ix ◽  
Factor Vii ◽  
Unesterified Fatty Acid ◽  
Factor Xii ◽  
Factor X ◽  
Factor Xi ◽  
Activated Factor Vii ◽  
Normal Mean

SummaryAbetalipoproteinaemia is a rare disorder of apolipoprotein B metabolism associated with extremely low plasma concentrations of triglyce-ride. To discover whether the general positive association between factor VII and triglyceride levels extends to this condition, 5 patients were compared with 18 controls. All patients had a triglyceride below 100 μmol/l. Plasma unesterified fatty acid concentration was normal. Although factor IX activity was only slightly reduced (mean 88% standard) and factor IX antigen was normal, mean activated factor VII in patients was strikingly reduced to 34% of that in controls, a level similar to that found in haemophilia B. The patients’ mean factor VII activity and factor VII antigen were also significantly reduced to 54% and 63% of those in controls, respectively. Mean factor XI activity and tissue factor pathway inhibitor activity were reduced in patients to 70% and 75% of control values respectively, while factor XII, factor XI antigen, factor X, prothrombin and protein C were normal.

Advanced inoperable type B3 thymoma: Monitoring of a novel therapeutic approach with radio-chemo therapy and sorafenib by FDG-PET and CT

2010 ◽  
Vol 49 (05) ◽  
pp. N41-N43
Author(s):  
T. Winder ◽  
A. Schuster ◽  
A. Becherer ◽  
K. Gasser ◽  
A. De Vries ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Therapeutic Approach ◽  
Novel Therapeutic

The Strong Positive Correlation between Factor VII Clotting Activity Using Bovine Thromboplastin and the Activated Factor VII Level

1995 ◽  
Vol 73 (03) ◽  
pp. 429-434 ◽  
Author(s):  
Kazuomi Kario ◽  
Takefumi Matsuo ◽  
Reiko Asada ◽  
Toshiyuki Sakata ◽  
Hisao Kato ◽  
...  
Keyword(s):  
Risk Factor ◽  
Bovine Brain ◽  
Factor Vii ◽  
Rabbit Brain ◽  
Strong Positive Correlation ◽  
Chromogenic Substrate ◽  
Moderate Correlation ◽  
Positive Correlation ◽  
Activated Factor Vii

SummaryWe compared factor VII clotting activity (FVIIc) assays using different thromboplastins to determine which is the most sensitive for activated FVII (FVIIa) or for FVII antigen (FVIIag). FVIIc levels were measured using thromboplastins derived from bovine brain (FVIIc Bov), human placenta (FVIIc Hum), and rabbit brain (FVIIc Rab). FVIIa levels were measured by fluorogenic assays using human soluble tissue factor (rsTF) or bovine rsTF. We also measured FVII activity by an amidolytic assay (FVIIc:am Hum) using human thromboplastin and a chromogenic substrate for thrombin. FVIIag levels were determined by ELISA. In the FVIIa assay, the reaction time obtained from using bovine rsTF was shorter than that with human rsTF, suggesting that the interaction of plasma FVIIa with bovine rsTF was stronger than with human rsTF. The plasma FVIIa levels measured using human rsTF and bovine rsTF were almost the same (r=0.947, p<0.0001). Among the three FVIIc assays, FVIIc Bov had the strongest positive correlation with the plasma FVIIa level (r=0.886, p<0.000l), but had no correlation with FVIIag. An increase of 1 ng/ml in the plasma FVIIa level yielded a 27.9% increase of FVIIc Bov. Plasma FVIIc Hum and FVIIc:am Hum showed moderate correlations with both FVIIa (r=0.520, p<0.02 and r=0.569, p<0.01, respectively) and FVIIag (r=0.438, p<0.05 and r=0.468, p<0.05, respectively). FVIIc Rab had the lowest correlation with FVIIa (r=0.367, p<0.1), but had a moderate correlation with FVIIag (r=0.436, p<0.05). After in vitro cold activation, FVIIc Bov levels increased the most and FVIIc:am levels showed the least change. These findings indicate that consideration of the thromboplastin used for assay is necessary when assessing the clinical significance of FVII activity as a cardiovascular risk factor.

A Comparison of Methods for the Measurement of Activated Factor VII

1992 ◽  
Vol 68 (03) ◽  
pp. 301-305 ◽  
Author(s):  
S Kitchen ◽  
R G Malia ◽  
F E Preston
Keyword(s):  
Factor Viia ◽  
Epidemiological Studies ◽  
Factor Vii ◽  
Haemophilia A ◽  
Reference Ranges ◽  
Activated Factor Vii ◽  
Normal Individuals ◽  
Antigen Assay ◽  
Activity State ◽  
Almost All

SummaryA number of different methods are available for the measurement of factor VIIa. Almost all of these employ ratios of two different measurements of factor VII. In order to determine which is the most sensitive to activated factor VII we have compared currently available methods in the following groups: two patients with haemophilia A following treatment with activated recombinant factor VII (rVII a); 6 normal plasmas during cold promoted activation of factor VII; normal individuals (n = 23); and patients with unequivocal disseminated intravascular coagulation (DIC, n = 19). Factor VII was measured in an amidolytic assay (VII: Amid) and an antigen assay (VII:Ag). Clotting activity was measured using rabbit (VII:C Rab), human (VII:C Hum) and bovine (VII:C Bov) thromboplastin.Of the clotting assays the most sensitive to the presence of factor VIIa was that which utilised bovine thromboplastin. Amidolytic and immunological measurements were unaffected by the activity state of factor VII. The ratios VII:C Rab/VII: Ag and VII:C Rab/VII:Amid were insensitive to activated factor VII. The ratios most sensitive to the presence of factor VII a were VII:C Bov/VII: Amid and VII: C Bov/VII:Ag. The ratios VII:C Bov/VII:C Rab and VII:C Bov/VII:C Hum are less sensitive but have the advantage for epidemiological studies of narrower reference ranges.

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