Unknown

Dataset Information

0

Recombinant canine B-domain-deleted FVIII exhibits high specific activity and is safe in the canine hemophilia A model.


ABSTRACT: Production of recombinant B-domain-deleted canine factor VIII (cFVIII-BDD) unexpectedly revealed superior protein yields with 3-fold increased specific activity relative to human FVIII-BDD (hFVIII-BDD). We also determined that activated cFVIII-BDD is more stable than activated hFVIII-BDD. Furthermore, cFVIII-BDD is efficient at inducing hemostasis in human plasma containing FVIII inhibitors. Infusion of cFVIII-BDD in hemophilia A dogs resulted in correction of the disease phenotype with a pharmacokinetic profile similar to clinical experience with hFVIII-BDD. Notably, immune tolerance challenges with cFVIII-BDD in young and adult hemophilia A dogs did not induce the formation of neutralizing or nonneutralizing antibodies to cFVIII. These data establish the framework to quantitatively investigate the efficacy and safety in preclinical studies of novel therapies for hemophilia A.

SUBMITTER: Sabatino DE 

PROVIDER: S-EPMC2925478 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

Recombinant canine B-domain-deleted FVIII exhibits high specific activity and is safe in the canine hemophilia A model.

Sabatino Denise E DE   Freguia Christian Furlan CF   Toso Raffaella R   Santos Andrey A   Merricks Elizabeth P EP   Kazazian Haig H HH   Nichols Timothy C TC   Camire Rodney M RM   Arruda Valder R VR  

Blood 20090921 20


Production of recombinant B-domain-deleted canine factor VIII (cFVIII-BDD) unexpectedly revealed superior protein yields with 3-fold increased specific activity relative to human FVIII-BDD (hFVIII-BDD). We also determined that activated cFVIII-BDD is more stable than activated hFVIII-BDD. Furthermore, cFVIII-BDD is efficient at inducing hemostasis in human plasma containing FVIII inhibitors. Infusion of cFVIII-BDD in hemophilia A dogs resulted in correction of the disease phenotype with a pharma  ...[more]

Similar Datasets

| S-EPMC4775845 | biostudies-other
| S-EPMC7786582 | biostudies-literature
| S-EPMC4265842 | biostudies-literature
| S-EPMC4650998 | biostudies-literature
| S-EPMC4183744 | biostudies-literature
| S-EPMC6700041 | biostudies-literature
| S-EPMC6470126 | biostudies-literature
| S-EPMC6960468 | biostudies-literature
| S-EPMC3070093 | biostudies-other
| S-EPMC7536163 | biostudies-literature