Survival rates after allogeneic hematopoietic cell transplantation (HCT) for Fanconi anemia (FA) have increased dramatically since 2000. However, the use of autologous stem cell gene therapy, whereby the patient's own blood stem cells are modified to express the wild-type gene product, could potentially avoid the early and late complications of allogeneic HCT. Over the last decades, gene therapy has experienced a high degree of optimism interrupted by periods of diminished expectation. Optimism stems from recent examples of successful gene correction in several congenital immunodeficiencies, whereas diminished expectations come from the realization that gene therapy will not be free of side effects. The goal of the 1st International Fanconi Anemia Gene Therapy Working Group Meeting was to determine the optimal strategy for moving stem cell gene therapy into clinical trials for individuals with FA. To this end, key investigators examined vector design, transduction method, criteria for large-scale clinical-grade vector manufacture, hematopoietic cell preparation, and eligibility criteria for FA patients most likely to benefit. The report summarizes the roadmap for the development of gene therapy for FA.
Bibliographical noteFunding Information:
The first meeting of an International Fanconi Anemia Gene Therapy Working Group, held on 16 November 2010, was organized and funded by the Fanconi Hope Charitable Trust, UK, and the Fanconi Anemia Research Fund, OR, USA. This meeting, hosted by Adrian Thrasher at the Institute of Child Health and chaired by Jakub Tolar from the University of Minnesota, brought together leading gene therapy and FA experts from across the globe to create an action plan for gene therapy trials in FA.
The authors would like to thank the Fanconi Anemia Research Fund, the Fanconi Hope Charitable Trust, the Spanish Association on FA, and the Children’s Cancer Research Fund, Minnesota. We thank Grover C. Bagby for useful comments on the manuscript. J.T. is supported by the Fanconi Anemia Research Fund, Children’s Cancer Research Fund, Minnesota, and the Albert D. and Eva J. Corniea Chair for clinical research. J.A.B. and P.R. are supported by grants from European Commision (FP7, Ministries of Science and Innovation and Health, Genoma España, and Fundación Botín). H.H. is supported by the DFG SPP1230, the BMBF networks for Inherited Bone Marrow Failure Syndromes, the Foamyviral Network for Genetic Therapy of FANCA, and R01 CA155294-01 and STTR R41HL099150. A.G. is supported by a grant from Genoma España, Madrid, Spain and by AFM (French Muscular Dystrophy Association), Evry, France. M.C.C. is supported by the Association Française contre les Myopathies (AFM) and Assistance Publique–Hôpitaux de Paris Direction de la Recherche Clinique. H.P.K. is supported by National Institutes of Health grants HL85693, DK56465, and HL36444. H.P.K. is a Markey Molecular Medicine Investigator and recipient of José Carreras/E. Donnall Thomas Endowed Chair for Cancer Research. Research in L.N. lab is supported by Telethon, the European Research Council, the European 7th Framework Program for Life Sciences, and the Italian Ministries of Health and of Scientific Research. E.V. is supported by grants from the European 7th Framework Program for Life Sciences and French grants (AFM and ANR). A.J.T. receives funding from The Wellcome Trust and Great Ormond Street Children’s Charity.