European Union Support of Gene Therapy Research: A Success Story
Authors: David Gancberg, Charles Kessler, Arnd Hoeveler, Ruxandra Draghia-Akli
Journal: Molecular Therapy (2012)

Research, education, and innovation are key tools to boost growth and employment in the European Union in the context of a global economy. Gene therapy research in Europe presently holds a leading position internationally. Recognizing that the development of effective and safe gene therapy protocols and their translation into products for patients is a lengthy and multidisciplinary process, over the past 15 years the European Union has supported collaborative efforts in gene transfer and gene therapy research amounting to more than €272 million distributed among 94 projects. The research teams—some of which include presidents of the European Society of Gene and Cell Therapy and European Research Council grant recipients—have published extensively and patented new tools for gene transfer and therapy. Investment in this field by the European Union has paid off and has led to new clinical trials in Europe and beyond. The recent potential therapeutic avenues generated by the use of induced pluripotent stem cells have reinforced interest in gene transfer technology. In combination with the deciphering of the human genome and advances in genetic testing and molecular diagnostics, new gene transfer technology should accelerate the development of personalized medicine and, in the event of discovery of a new molecular target, should speed up application of such targets in the clinic. Although the regulatory processes for engineered cell-based therapies and product marketing authorization slow the translation from bench to bedside, the safety of gene transfer vectors has improved markedly in recent years. The European Medicines Agency's recent approval of Glybera as the first gene therapy medicinal product in the European Union1Ylä-Herttuala S Endgame: Glybera finally recommended for approval as the first gene therapy drug in the European Union.Mol Ther. 2012; 20: 1831-1832Abstract Full Text Full Text PDF PubMed Scopus (300) Google Scholar underlines the progress made over the years and strengthens the promise of the field for new treatments of rare and more common dis­orders that currently lack effective therapies. The European Union supports research and technology development via multiannual Framework Programmes, and each year it publishes an online Work Programme calling for research proposals in particular areas, such as rare, chronic, or infectious diseases, biotechnologies and medical devices, diagnostics, or cancer (http://ec.europa.eu/research/participants/portal/page/cooperation#health). Researchers worldwide can participate in these projects, provided that the projects include collaborators from at least three European Union member states or associated countries. Global stakeholders such as the World Health Organization or public–private partnerships, civil society, nongovernmental organizations, patient organizations, or individuals are also welcome. Notably, European funding programs are fully open to US researchers, based on a mutual agreement between the European Union and the National Institutes of Health.2Zerhouni EA Potocnik J European Union and NIH Collaborate [letter].Science. 2008; 322: 1048Crossref PubMed Scopus (8) Google Scholar A majority of the ongoing projects represent multidisciplinary collaborations between academia, clinicians, and industry. Moreover, specific calls for proposals are designed to attract participation of small and medium-sized enterprises (SMEs) by requesting industrial leadership of the project, a limited lifetime (up to 3 years), and a substantial budget allocation (up to 50%) to industry. Evaluations of proposals are performed by highly recognized international experts from both academia and industry, and typically involve two stages. During the first stage both the scientific and technological merit, as well as the potential societal impact of projects, are evaluated. Participants in the successful projects are then requested to submit a more detailed work program for the second stage. These are then judged on three criteria: science and technology, impact, and implementation. Successful candidates participate in a negotiation phase during which the experts’ scientific, ethical, and administrative recommendations are included in the project before the grant agreement is signed. In the 1990s, successful projects addressed basic research and specific problems such as vector safety, the delivery of transgenes to specific cells, the control of transgene expression, and the development of new preclinical in vivo models and of new cell lines for viral production. Today, as we are reaching the end of the 7th Framework Programme (FP7, 2007–2014; Table 1), most of the latest calls for proposals require as eligibility conditions the performance of clinical trial(s) and substantial involvement of SMEs. Differences in regulations between countries remain an impediment to international collaboration involving clinical studies, and efforts toward harmonization and mutual recognition of ethical and regulatory processes should facilitate future studies.Table 17th Framework Programme collaborative projects involving gene transfer and gene therapy (as of September 2012)AcronymNo. of partnersStarting date (month/year)EU contribution (euro; million)Total cost (euro; million)Targeted disease(s) or organ(s)Clinical trialWebsiteMicroEnviMet903/20083. 04. 3Metastatic niche and cancer stem cellsNohttp://www.microenvimet.euCrumbs in sight604/20083. 04. 0Retinitis pigmentosa, Leber congenital amaurosisNohttp://crfb.univ-mrs.fr/CrumbsEuclyd605/20083. 03. 9Lysosomal storage diseases (Gaucher, Pompe, MPS VI, multiple sulfatase deficiency)Nohttp://www.euclyd.euBrainCAV1010/20083. 04. 4MPS VII, ParkinsonNohttp://www.braincav.euNEUGENE610/20083. 04. 0ParkinsonNohttp://www.neugene.euLiv-ES710/20083. 04. 2LiverNohttp://www.liv-es.euAAVEYE411/20083. 04. 0Retinitis pigmentosa, Leber congenital amaurosisNohttp://www.aaveye.euPersist2401/200911. 214. 8Hemophilia, lysosomal storage diseases (Krabbe, Pompe), SCID-X1Nohttp://www.persist-project.euOptiStem1901/200912. 016. 8DMD; epithelial, ocular surface, and oral mucosa disordersYeshttp://www.optistem.orgTreatrush1102/20106. 08. 0Usher syndrome types I and IINohttp://www.treatrush.euLeukoTreat2403/20106. 09. 0LeukodystrophiesNohttp://leukotreat.euGAMBA909/20103. 24. 1Bone and cartilageNohttp://www.gamba-project.euCELL-PID1911/201011. 915. 7Wiskott-Aldrich syndrome, SCID-X1, CGD, IPEX, HLH, ADA-SCID, Omenn syndrome, Artemis deficiencyYeshttp://www.cell-pid.euAIPGENE701/20113. 34. 4Acute intermittent porphyriaYeshttp://www.aipgene.orgGeneGraft703/20115. 06. 3Epidermolysis bullosaYeshttp://genegraft.euBIOMAGSCAR801/20125. 36. 8Restenosis and thrombosisYes http://www.euram.ltd.uk/BIOMAGSCARTotal176—84. 9114. 7ADA-SCID, adenosine deaminase severe combined immumunodefidency; CGD, chronic granulomatous disease; DMD, Duchenne muscular dystrophy; HLH, hemophagocytic lymphohistiocytosis; IPEX, immunodysregulation polyendocrinopathy enteropathy X-linked syndrome; MPS VI, mucopolysaccharidosis type VI; SCID-X1, X-linked SCID. Open table in a new tab ADA-SCID, adenosine deaminase severe combined immumunodefidency; CGD, chronic granulomatous disease; DMD, Duchenne muscular dystrophy; HLH, hemophagocytic lymphohistiocytosis; IPEX, immunodysregulation polyendocrinopathy enteropathy X-linked syndrome; MPS VI, mucopolysaccharidosis type VI; SCID-X1, X-linked SCID. Under FP7, to date, 16 collaborative projects involving gene transfer and gene therapy research have been supported with a total budget of over €84.9 million (Table 1). They represent a total of 180 participating organizations, of which 16% are SMEs, creating a unique opportunity for synergy between research teams from the public and private sectors (Figure 1a). Although most participants are based in Europe (Figure 1b), more than one-third of the projects include at least one participant outside the European Union. The 2012 Work Programme, published in July 2011, advertised calls for proposals for clinical trials in gene therapy, DNA vaccination, oligonucleotide and RNA transfer, and also targeted proposals pertaining to rare diseases. As a result, approximately €46 million will be granted during 2012 to eight new projects addressing chronic granulomatous disease, mucopolysaccharidosis type VI, Fanconi's anemia, β-thalassemia, or muscular dystrophy, and more frequently occurring disorders such as fetal growth restriction, age-related macular degeneration, and cancer. Each involves significant participation by SMEs and industry. Thanks to the reinforced policy of SME involvement in FP7, SME participation in gene transfer projects now represents more than 13% of the European Union budget contribution, compared with less than 6% in the previous Framework Programmes. The next European strategic framework for research and innovation for the period 2014–2020, Horizon 2020, will continue to support the development of innovative tools, technologies, and SME-targeted topics. Possible applications of the technology lie not only in the treatment of rare disorders but also in major health problems related to a rapidly aging European population such as cancer and diabetes, as well as cardiovascular and neurodegenerative disorders. The authors thank Juan Carlos Del Rio for the statistical analysis. The views expressed in this publication are the sole responsibility of the authors and do not necessarily reflect the views of the European Commission. Neither the European Commission nor any person acting on behalf of the Commission is responsible for the use that might be made of the information contained in this article.