Advancements in gene transfer-based therapy for hemophilia A

• Type of Material: Article
• Authors: Christopher Doering, Emory University; Harold Trent Spencer, Emory University
• Language: English
• Date: 2009-12
• Publisher: Taylor & Francis: STM, Behavioural Science and Public Health Titles - No Open Select
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009 Expert Reviews Ltd
• Final Published Version (URL): http://informahealthcare.com/doi/abs/10.1586/EHM.09.63
• Title of Journal or Parent Work: Expert Review of Hematology
• ISSN: 1747-4086
• Volume: 2
• Issue: 6
• Start Page: 673
• End Page: 683
• Grant/Funding Information: National Heart, Lung, and Blood Institute : NHLBI
• Keywords: transposon; adenovirus; hematopoietic stem cell transplantation; viral vector; gene therapy; adeno-associated virus; hemophilia A; lentivirus; oncoretrovirus; factor VIII
• Research Categories: Health Sciences, Pathology; Health Sciences, Oncology

Abstract

Gene therapy has promised clinical benefit to those suffering with hemophilia A, but this benefit has not yet been realized. However, during the past two decades, basic and applied gene therapy research has progressed and the goal of gene therapy for hemophilia A is once again in our sights. The hemophilia A patient population suffers from a disease that requires invasive, lifelong management, is exorbitantly expensive to treat, has geographically limited treatment access and can become untreatable due to immune reactions to the treatment product. Subsequent to the cloning of the factor VIII gene and cDNA in the early 1980s, academic and commercial research laboratories began to pursue gene transfer-based therapies to supplement or supplant the available protein replacement therapy. However, to date, clinical trials for gene therapy of hemophilia A have been unsuccessful. Three trials have been conducted with each having tested a different gene-transfer strategy and each demonstrating that there is a considerable barrier to achieving sustained expression of therapeutic amounts of factor VIII. Recent progress has been made in gene-transfer technology and, relevant to hemophilia A, towards increasing the biosynthetic efficiency of factor VIII. These advances are now being combined to develop novel strategies to treat and possibly cure hemophilia A.