Can we improve on nature? "Super molecules" of factor VIII.
Treatment of haemophilia A requires frequent infusion of plasma- or recombinant-derived factor VIII. This regimen is limited due to the high cost and inconvenient access to peripheral veins. In addition, patients frequently develop inhibitory antibodies that limit available therapeutic regimens. Two major advances in factor VIII research over the past 15 years were the ability to isolate homogeneous preparations of factor VIII and the isolation of the factor VIII gene that provided for a detailed biochemical and structural characterization of the factor VIII molecule. With an increased understanding of the requirements for factor VIII function, studies have attempted to produce improved factor VIII molecules for replacement therapy. These findings have produced forms of factor VIII that are more efficiently produced, that are less immunogenic, and that have higher specific activity. The future will see the engineering of novel factor VIII molecules with increased therapeutic efficiency while minimizing inhibitor antibody development. In addition, there are now structural models of factor VIII available that should in the future direct development of novel peptidomimetics that may eventually overcome the requirement for replacement therapy with factor VIII protein.
Kaufman
R J
RJ
Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor 48109, USA. kaufmanr@umich.edu
Pipe
S W
SW
D000818:Animals; D005169:Factor VIII / Q000235:genetics* / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D015202:Protein Engineering; D013329:Structure-Activity Relationship
D005169:Factor VIII