In:
Haematologica, Ferrata Storti Foundation (Haematologica), Vol. 105, No. 9 ( 2019-11-07), p. 2335-2340
Kurzfassung:
Rendering coagulation factor X sensitive to thrombin was proposed as a strategy that can bypass the need for factor VIII. In this paper, this non-replacement strategy was evaluated in vitro and in vivo in its ability to correct factor VIII but also factor IX, X and XI deficiencies. A novel modified factor X, named Actiten, was generated and produced in the HEK293F cell line. The molecule possesses the required post-translational modifications, partially keeps its ability to be activated by RVV-X, factor VIIa/tissue factor, factor VIIIa/factor IXa and acquires the ability to be activated by thrombin. The potency of the molecule was evaluated in respective deficient plasmas or hemophilia A plasmas, for some with inhibitors. Actiten corrects dose dependently all the assayed deficient plasmas. It is able to normalize the thrombin generation at 20 μg/mL showing however an increased lagtime. It was then assayed in a rabbit antibody-induced model of hemophilia A where, in contrast to recombinant factor X wild-type, it normalized the bleeding time and the loss of hemoglobin. No sign of thrombogenicity was observed and the generation of activated factor X was controlled by the anticoagulation pathway in all performed coagulation assays. This data indicates that Actiten may be considered as a possible non replacement factor to treat hemophilia's with the advantage of being a zymogen correcting bleedings only when needed.
Materialart:
Online-Ressource
ISSN:
1592-8721
,
0390-6078
DOI:
10.3324/haematol.2019.219865
Sprache:
Unbekannt
Verlag:
Ferrata Storti Foundation (Haematologica)
Publikationsdatum:
2019
ZDB Id:
2186022-1
ZDB Id:
2030158-3
ZDB Id:
2805244-4
