Gene therapy for haemophilia: prospects and challenges to prevent or reverse inhibitor formation
Version of Record online: 7 NOV 2011
Published 2011. This article is a US Government work and is in the public domain in the USA.
British Journal of Haematology
Volume 156, Issue 3, pages 295–302, February 2012
How to Cite
Scott, D. W. and Lozier, J. N. (2012), Gene therapy for haemophilia: prospects and challenges to prevent or reverse inhibitor formation. British Journal of Haematology, 156: 295–302. doi: 10.1111/j.1365-2141.2011.08925.x
- Issue online: 11 JAN 2012
- Version of Record online: 7 NOV 2011
- factor VIII (FVIII);
- factor IX (FIX);
- gene therapy;
- immune tolerance
Monogenic hereditary diseases, such as haemophilia A and B, are ideal targets for gene therapeutic approaches. While these diseases can be treated with protein therapeutics, such as factor VIII (FVIII) or IX (FIX), the notion that permanent transfer of the genes encoding these factors can cure haemophilia is very attractive. An underlying problem with a gene therapy approach, however, is the patient’s immune response to the therapeutic protein (as well as to the transmission vector), leading to the formation of inhibitory antibodies. Even more daunting is reversing an existing immune response in patients with pre-existing inhibitors. In this review, we will describe the laboratory and clinical progress, and the challenges met thus far, in achieving the goal of gene therapy efficacy, with a focus on the goal of tolerance induction.