For Research Use Only. Not for Clinical Use.

Introduction of Hemophilia

Haemophilia is a rare genetic disease that results from mutations in the genes that code for proteins necessary for normal blood clotting factor VIII (hemophilia A) and factor IX (hemophilia B). About 30% of hemophilia cases occur sporadically at birth, and a few cases occur later in life (acquired hemophilia), with Hemophilia A being four times more frequent than Hemophilia B. Factor XI deficiency (originally called hemophilia C) is less common and in most cases, mild bleeding disorder, autosomally inherited, and particularly common in Ashkenazi Jews. The commonest inherited bleeding disorder is von Willebrand's disease, a defect in the quantity or quality of the von Willebrand factor, present in perhaps as many as 1% of the general population. This disorder is generally mild, but it is an important cause of menorrhagia in affected kindreds. An important point to note is that the diagnosis is not excluded by a normal coagulation screen. Congenital deficiencies of other coagulation factors are rare. These are autosomal recessive conditions that are therefore more prevalent in communities where consanguinity is common.

Fig. 1 Schematic model of coagulation in vivo. (Bolton-Maggs, 2003)

Application of Half-life Extended Drug in Hemophilia

Following the elimination of the problem of viral safety which dominated hemophilia replacement therapy up to 30 years ago, the attention of treaters and patients has shifted focus to new and improved options for the treatment of this group of disorders. During the last decade, numerous new recombinant Factor VIII and Factor IX concentrates have been introduced in hemophilia therapy, which has been characterized by molecular modifications allowing improvements for the establishment and tailoring of personalized treatment. Foremost among these has been the generation of several concentrates characterized by a more extended presence of the substituting Factor VIII or Factor IX molecule in the patients' circulation. These Extended half-lives (EHL) products demonstrate improved pharmacokinetics. The half-life is 1.43-1.53 fold and 2-3 fold for rFVIII and rFIX EHL products respectively, relative to the infusion of standard forms of FVIII and FIX. This leads to the possibility of increasing compliance to prophylaxis, with the availability of regimens made less demanding through lower infusion frequencies. This plethora of recombinant concentrates, old and new, has raised the possibility that all hemophilia patients may be adequately treated, given the detachment of product availability from the inevitably limited plasma supply.

Hemophilia still afflicts many people around the world up to now, however, drugs with longer half-lives offer hope for its future. Creative Biolabs briefly introduces hemophilia and relevant half-life extended drugs' application. We have established a comprehensive technology platform to help our customers accelerate relevant research. If you are looking for partners in half-life extension research or have any questions about our services, please feel free to contact us for more information.

Reference

1. Bolton-Maggs, P. H. and Pasi, K. J. Haemophilias A and B. Lancet. 2003, 361(9371): 1801-9.