Characterization of a recombinant factor IX molecule fused to coagulation factor XIII-B subunit.
Haemophilia
; 29(6): 1483-1489, 2023 Nov.
Article
in En
| MEDLINE
| ID: mdl-37707428
ABSTRACT
INTRODUCTION AND AIM:
Severe haemophilia B (HB) is characterized by spontaneous bleeding episodes, mostly into joints. Recurrent bleeds lead to progressive joint destruction called haemophilic arthropathy. The current concept of prophylaxis aims at maintaining the FIX level >3-5 IU/dL, which is effective at reducing the incidence of haemophilic arthropathy. Extended half-life FIX molecules make it easier to achieve these target trough levels compared to standard FIX concentrates. We previously reported that the fusion of a recombinant FIX (rFIX) to factor XIII-B (FXIIIB) subunit prolonged the half-life of the rFIX-LXa-FXIIIB fusion molecule in mice and rats 3.9- and 2.2-fold, respectively, compared with rFIX-WT. However, the mechanism behind the extended half-life was not known. MATERIALS ANDMETHODS:
Mass spectrometry and ITC were used to study interactions of rFIX-LXa-FXIIIB with albumin. Pharmacokinetic analyses in fibrinogen-KO and FcRn-KO mice were performed to evaluate the effect of albumin and fibrinogen on in-vivo half-life of rFIX-LXa-FXIIIB. Finally saphenous vein bleeding model was used to assess in-vivo haemostatic activity of rFIX-LXa-FXIIIB. RESULTS ANDCONCLUSION:
We report here the key interactions that rFIX-LXa-FXIIIB may have in plasma are with fibrinogen and albumin which may mediate its prolonged half-life. In addition, using the saphenous vein bleeding model, we demonstrate that rFIX-FXIIIB elicits functional clot formation that is indistinguishable from that of rFIX-WT.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Vascular Diseases
/
Hemostatics
/
Hemophilia B
/
Joint Diseases
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Haemophilia
Journal subject:
HEMATOLOGIA
Year:
2023
Document type:
Article
Affiliation country: