Prophylactic administration of glycoPEGylated factor IX provides protection and joint outcome superior to recombinant factor IX after induced joint bleeding.

Abstract

BACKGROUND:

Following induced joint hemorrhage, hemophilia B results in the abnormal persistence of iron deposition, inflammation, and neovascularity of the synovial tissue, as well as deterioration of the bone articular surface and strength. Previously, we demonstrated that a factor IX (FIX) replacement protein with extended circulating FIX activity, glycoPEGylated FIX nonacog beta pegol (N9-GP), could improve synovial and osteochondral parameters in F9 knockout mice when administered after joint injury.

OBJECTIVE:

We explored the use of N9-GP prior to unilateral joint hemorrhage and compared to unmodified recombinant FIX (rFIX).

METHODS:

Pharmacodynamics, histology, and microcomputed tomography were used to assess the effects of prophylactic administration of glycoPEGylated FIX.

RESULTS:

In comparison to rFIX, N9-GP significantly improved soft tissue histological parameters, as well as bone outcome at 2 weeks post injury, while performing equally in reduction of blood present in the joint space assessed 1 day after injury.

CONCLUSIONS:

These results indicate that, in comparison to rFIX, the prophylactic use of extended half-life FIX provides superior protection from bleeding-induced joint damage, manifested by improved correction of histologic parameters.

• Authors: Junjiang Sun, Eric W Livingston, Mie L Broberg, Peter B Johansen, Carsten D Ley, Tom Knudsen, Mirella Ezban, Ted Bateman, Paul E Monahan, Sarah Taves
• Journal: Journal of thrombosis and haemostasis : JTH (J Thromb Haemost) Vol. 17 Issue 8 Pg. 1240-1246 (08 2019) ISSN: 1538-7836 [Electronic] England
• PMID: 31148392 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 International Society on Thrombosis and Haemostasis.

Chemical References

• Hemostatics
• Recombinant Proteins
• nonacog beta pegol
• Polyethylene Glycols
• Factor IX

Topics

• Animals
• Disease Models, Animal
• Drug Administration Schedule
• Factor IX (administration & dosage, genetics, metabolism, pharmacokinetics)
• Half-Life
• Hemarthrosis (diagnostic imaging, drug therapy, genetics, metabolism)
• Hemophilia B (drug therapy, genetics, metabolism)
• Hemostatics (administration & dosage, pharmacokinetics)
• Joints (diagnostic imaging, drug effects, pathology)
• Mice, Inbred C57BL
• Mice, Knockout
• Polyethylene Glycols (administration & dosage, pharmacokinetics)
• Recombinant Proteins (administration & dosage, pharmacokinetics)