Hematopoietic Gene Therapy – HemGenTher

In recent years, the field of gene therapy has surmounted major hurdles that were preventing the development of this revolutionary therapeutic modality. Gene transfer to hematopoeitc stemcells (HSCs) has led the way with proof-of-principle of efficacy in clinical trials for several inherited diseases that include the X-SCID syndrome, adrenoleukodystrophy and beta-thalassemia. As for other therapeutics, side effects or molecular anomalies have nevertheless occured in a limited number of patients as a result of the genotoxicity of integrative vectors.
Before hematopoietc gene therapy can be broadly available to patients, key obstacles remain. Itwould indeed be highly desirable to expand HSCs safely to decrease the time to engraftment, lower the dose of pre-conditioning regimen, and allow the use of fewer and more purified transduced cells in an effort to decrease the risk of genotoxicity. In addition, ex vivo HSC expansion would make it possible to apply selection to increase therapeutic efficacy. To this aim, ex vivo selection reagents and approaches need to be further developed, especially in conjunction with conditional suicide to maximize safety. Finally, achievingtargeted chromosomal integration of lentiviral vectors at high efficiency to non-hazardous loci would be extremely significant. The objectives and tasks of this proposal tackle these key issues.
France has played a key role in the field of gene therapy, as the three aforementioned clinicaltrials were performed in Paris. In addition, major efforts such as AFM, Généthon and Imagine are highly valuable. This Industrial Chair is ideally suited to this field, since joint academy-industry R&D is acutely needed to move the field forward and maintain France’s pole position. CEA as an « EPIC » is especially well suited, with its scientific force and non-human primate facility.
The candidate for this industrial chair, Prof. Philippe Leboulch, is a world-renowned expert in gene therapy. After publishing major preclinical advances (e.g., Nat Med 1999, Science 2000, Science 2001), he is the leader of the first clinical trial for the gene therapy of the ?-hemoglobinopathies (Nature 2010), qualified by many as the most important recent milestone in the field (see Nat Biotech 2011;2:121-28). He was also recently featured for his international work (see Nat Med 2011;17:912-15). After 20 years on the Harvard Medical School faculty, he now heads the Institute of Emerging Diseases and Innovative Therapies (iMETI) of the CEA, in liaison with INSERM and the University of Paris. P. Leboulch also has an extensive experience in the biotechnology field. He was member of the Board of the Evry Genopole as well as Founder and CSO of Genetix Pharm. (recently renamed bluebird bio) where he contributed in raising over $90 million from Johnson & Johnson and renowned venture capitalists.
The industrial partner of this Chair, bluebird bio, holds an enviable position in the field of gene therapy. It has accumulated a broad and dominant patent portfolio in therapeutic lentiviral vectors and raised $70 million in the past year. It has already established a French subsidiary at the CEA. At a time when bluebird bio is considering various international joint opportunities with academic centers and when the CEA welcomes such an effort but no longer has the financial means to allocate funds due to the current economic crisis, this Industrial Chair program is extremely important to solidify this partnership and continue to develop the industry of Gene Therapy in France.