The major
therapy for
haemophilia is plasma derived or recombinant
clotting factors which are evolving steadily to increase potency, stability and half-life. Research in the area of
haemophilia therapeutics, however, is not restricted only to modifications in the recombinant products, but alternate therapeutic strategies are being developed which are in different phases of experimental and clinical trials. This chapter reviews the diverse molecular innovations which are being developed for alternate therapeutic approaches in
haemophilia. The data is mainly extracted from the literature and the Conference abstracts. Some of the novel therapeutic approaches include inhibition of
anticoagulant pathway factors (activated
protein C,
antithrombin,
tissue factor pathway inhibitor) by
monoclonal antibodies,
peptide inhibitors,
DNA or
RNA aptamers, use of variant
coagulation factors (
factor Xa,
factor Va) which are more resistant to inactivation or enzymatically more active and antibody-mediated
therapy including a humanized anti-
factor IXa/X bispecific antibody mimicking
factor VIII. Other approaches include
nonsense mutation suppression, induction of prothrombotic microparticles by
P-selectin-
immunoglobulin chimeras, suppression of fibrinolytic potential either by
antifibrinolytics or by the use of mutant molecules of fibrinolytic inhibitors. Few products are proposed as 'stand alone' treatment for
haemophilia, while a few can be used as adjuvant
therapies to recombinant factors with an aim to reduce the amount of factor intake. All efforts are underway to produce an alternate, novel
drug for
haemophilia which will have an increased half-life, subcutaneously
injectable, non-immunogenic and effective both in the presence and absence of inhibitors.