The genetic blood disorder hemophilia B, caused by factor IX (FIX) deficiency, can be effectively controlled with gene replacement therapies, particularly when used for prevention.
But because barriers to prophylaxis that include intravenous use, frequent dosing and medical costs are many, new research for better therapies is emerging.
Researchers at the University of Wisconsin School of Medicine and Public Health in Wisconsin, have reviewed the evolution of FIX replacement therapy and products that deliver FIX to patients or that help control the disease symptoms.
The study, “New developments in the management of moderate-to-severe hemophilia B,” was published in the Journal of Blood Medicine.
Hemophilia B can be classified as severe, moderate, or mild, depending on the activity of FIX.
The severe hemophilia is characterized by spontaneous bleeding into joints and muscles, causing long-term disabilities; a moderate case is characterized by spontaneous bleeds and prolonged bleeding when exposed to surgery or traumas; and the mild form of which significant bleeding occurs at surgery or trauma, but rarely causes spontaneous bleeds.
Currently, researchers have been working develop FIX proteins to discourage hemorrhage, that are highly active and can be kept in circulation for longer periods. Other approaches that act on other proteins of the coagulation pathways are also under development.
Following a huge change in treatment from 1997 when the administration of recombinant FIX, produced by cells in culture, was approved by the Food and Drug Administration (FDA), researchers have now developed recombinant forms of FIX that have increased half-lives.
Two of them, FIXFc and rIX-FP, represent proteins in which FIX was fused respectively with a part of the immunoglobulin G1 (IgG1) or with albumin, which result in proteins that are recycled at a slower rate.
Another product is a modification of FIX with pegylation, which is known to increase the half-lives and live animal test activity of other therapeutic proteins.
Clinical trial of the three products in hemophilia B patients have shown excellent efficacy and the patients required less doses than with the original recombinant protein.
Other strategies designed to rebalance blood coagulation hemophilia treatment include using antibodies that inhibit proteins that are themselves inhibitors of the coagulation pathway; or gene therapies that knockdown the antithrombin gene, restoring the normal levels of thrombin, a coagulation factor.