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

Denise E. Sabatino, Christian Furlan Freguia, Raffaella Toso, Andrey Santos, Elizabeth P. Merricks, Haig H. Kazazian, Timothy C. Nichols, Rodney M. Camire, Valder R. Arruda

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)4562-4565
Number of pages4
JournalBlood
Volume114
Issue number20
DOIs
StatePublished - Nov 12 2009

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Sabatino, D. E., Freguia, C. F., Toso, R., Santos, A., Merricks, E. P., Kazazian, H. H., Nichols, T. C., Camire, R. M., & Arruda, V. R. (2009). Recombinant canine B-domain-deleted FVIII exhibits high specific activity and is safe in the canine hemophilia A model. Blood, 114(20), 4562-4565. https://doi.org/10.1182/blood-2009-05-220327