It is also not associated with adverse reactions, such as thrombocytopenia,

allergic reactions or the development of resistance through antibody formation and thus it is suitable for home treatment. Although, Hyate:C is no longer available, a recombinant factor VIII has been developed as a collaboration between Ipsen, Inspiration and Emory University. This is produced at a facility near Boston in the United States of America. There is a high degree of sequence and functional homology between human and porcine factor VIII. Both human and porcine factor VIII share a common sequence of A1–A2–B–A3–C1–C2 domains and both molecules are cleaved by thrombin to form a dimer composed of a light and heavy chain [24]. selleck kinase inhibitor OBI-1 is a recombinant B-domain deleted form of porcine factor VIII synthesized in baby hamster kidneys cells grown in a serum-free medium. It does not contain any porcine von Willebrand factor. Phase III clinical trials in patients with acquired haemophilia and congenital haemophilia

A complicated by alloantibodies are underway [25]. A goal of future research will be to attempt to produce a porcine factor VIII molecule, which is even less antigenic than the natural wild type. This could be done by substitution of specific amino acids through genetic engineering, eliminating those that seem to be particularly LY2109761 nmr immunogenic, or creating human/porcine hybrid constructs [26,27]. Such modified molecules could then conceivably be used to treat noninhibitor patients too, or at least as treatment in the early period soon after diagnosis which is known to be the peak risk period MCE for inhibitor development. There is already quite a wealth of information available

on which parts of the porcine and human factor VIII molecules are particularly immunogenic. The antibody response to the individual FVIII domains in haemophilic mice immunized with human or porcine FVIII has provided important information [28].The overall immunogenicity of human and porcine FVIII is similar, but significant differences in domain recognition have been identified. Anti-A2 and anti-C2 antibodies constitute the majority of inhibitors in both the human and porcine FVIII groups, similar to inhibitors that develop in humans. The proportions of anti-A2 or anti-C2 antibodies were not significantly different between the two groups in one study. However, the proportion of anti-C1 antibodies was significantly higher in the human FVIII group, whereas anti-A3 antibodies were more common in the porcine FVIII group. The differential immune response to human and porcine FVIII supports the view that it may be possible to reduce the immunogenicity of porcine (and human) FVIII by mutagenesis at specific sites, within the A2, A3 and C1 domains. In a final twist to this tale, it appears that pigs may be able to provide us with human coagulation proteins like factor VIII and IX [29,30].