New Approaches to Haemophilia Treatment – Recombinant and Transgenic Concentrates, Gene Therapy and Engineered Coagulation Factors

Overview

Plasma-derived concentrates of coagulation factors VIII and IX allow for effective treatment of haemophilia A and B. Current problems associated with this therapy include induction of inhibitory antibody directed towards coagulation factor (inhibitor), requirement of frequent intravenous application since childhood, very high price precluding utilisation of the treatment in developing countries and very low risk of transmission of known human infections. Cloning of factors VIII and IX allowed for application of recombinant technologies to address these problems. Small and large animal models have become available to test effectiveness and safety of novel treatments. The third generation recombinant concentrates of factors VIII and IX have recently been approved, which overcome the risk of transmission of a human infection. However, the problem of the inhibitory antibody response remains. Recombinant activated factor VIIa has become effective, safe but expensive alternative for treatment of patients with the inhibitor. High price of recombinant concentrates precludes their use in developing countries. Transgenic animals may in future allow for production of cheaper concentrates. Concluded clinical trials with therapeutic gene transfer in haemophilia A and B have shown that the approach is relatively safe, but not yet effective. Ongoing studies in vitro and in vivo are trying to improve the effectiveness. Engineered molecules of factors VIII and IX already tested in vitro and in vivo, on animal models may in future improve both classical and gene theraples. 

Key words:
haemophilia treatment, haemophilia animal models, recombinant concentrates, gene therapy, transgenic animals, engineered coagulation factors.