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Gene THERAPY PROJECT SYNOPSES Interested in European research? Research*eu is our quarterly magazine keeping you in touch with main developments (results, pro- grammes, events, etc.). It is available in English, French and German. A free sample copy or free subscription can be obtained from: European Commission Directorate-General for Research Information and Communication Unit B-1049 Brussels Fax (32-2) 29-58220 E-mail: [email protected] Internet: http://europa.eu.int/comm/research/rtdinfo/index_en.html EUROPEAN COMMISSION Directorate F – Health Unit F5 – Health Biotechnology Contact: Charles Kessler Office CDMA 2/188 Tel (32-2) 29 56112 Fax (32-2) 29 94693 E-mail: [email protected] EUROPEAN COMMISSION NEW THERAPIES EU-supported research in Genomics and Biotechnology for Health Sixth Framework Programme (2002-2006) Edited by Charles Kessler Directorate-General for Research 2007 Life Sciences, Genomics and Biotechnology for Health EUR 22841 NEW THERAPIES TABLE OF CONTENTS INTRODUCTION 11 REGeneratiVE MEDICINE 15 EuroStemCell THERAPEUSKIN European consortium for stem cell research 17 Ex vivo gene therapy for recessive dystrophic epi- dermlysis bullosa : preclinical and clinical studies GENOSTEM 44 Adult mesenchymal stem cells engineering for connective tissue disorders. From the bench to BetaCellTherapy the bed side 22 Beta cell programming for treatment of diabetes 47 OsteoCord Bone from blood: optimised isolation, characteri- EuroSTEC sation and osteogenic induction of mesenchy- Soft tissue engineering for congenital birth mal stem cells from umbilical cord blood 27 defects in children: new treatment modalities for spina bifida, urogenital and abdominal wall TherCord defects 52 Development and preclinical testing of cord blood-derived cell therapy products 30 SC&CR Application and process optimisation of human EPISTEM stem cells for myocardium reapair 57 Role of p63 and related pathways in epithelial stem cell proliferation and differentiation and in STEMSTROKE rare EEC-related syndromes. 32 Towards a stem cell therapy for stroke 61 Ulcer Therapy STEMS Gene transfer in skin equivalnts and stem cells: Preclinical evaluation of stem cell therapy in novel strategies for chronic ulcer repair and tis- stroke 64 sue regeneration 37 STROKEMAP Skintherapy Multipotent Adult Progenitor Cells to treat Stroke Gene therapy for Epidermolysis Bullosa: a model 67 system for treatment of inherited skin diseases. 41 RESCUE From stem cell technology to functional restora- tion after spinal cord injury 69 New Therapies – Table of contents 5 NEW THERAPIES TABLE OF CONTENTS GENE THERAPY 83 STEM-HD CLINIGENE Embryonic stem cells for therapy and exploration European Network for the Advancement of Clini- of mechanisms in Huntington Disease 72 cal Gene Transfer and Therapy 85 NEUROscreen CONSERT The discovery of future neuro-therapeutic Concerted Safety & Efficiency Evaluation of Ret- molecules 75 roviral Transgenesis in Gene Therapy of Inherited Diseases 92 myoamp Amplification of human myogenic stem cells in GIANT clinical conditions 77 Gene therapy: an Integrated Approach for Neo- plastic Treatment 98 CRYSTAL CRYo-banking of Stem cells for human Therapeu- BACULOGENES tic AppLicationp 80 Baculovirus vectors for gene therapy 102 THOVLEN Targeted Herpesvirus-derived Oncolytic Vectors for Liver cancer European Network 104 THERADPOX Optimised and novel oncolytic adenoviruses and pox viruses in the treatment of cancer: Virothera- py combined with molecular chemotherapy 107 RIGHT RNA Interference Technology as Human Thera- peutic Tool 110 ZNIP Therapeutic in vivo DNA repair by site-specific double-strand breaks 115 SNIPER Sequence Specific Oligomers for in vivo DNA Repair 118 Improved precision Improved precision of nucleic acid based therapy of cystic fibrosis 121 6 New Therapies – Table of contents NEW THERAPIES INTHER InVivoVectorTrain Development and application of transposons European labcourse: towards clinical gene thera- and site-specific integration technologies as py: preclinical gene transfer assessment 147 non-viral gene delivery methods for ex vivo gene- based therapies 124 IndustryVectorTrain European labcourse: advanced methods for in- Epi-Vector dustrial production, purification and characteri- Episomal vectors as gene delivery systems for sation of gene vectors 150 therapeutic application 129 PolExGene Biocompatible non-viral polymeric gene delivery systems for the ex vivo treatment of ocular and cardiovascular diseases with high unmet medical need 133 Magselectofection Combined isolation and stable nonviral trans- fection of hematopoietic cells ‘ a novel platform technology for ex vivo hematopoietic stem cell gene therapy 135 SyntheGeneDelivery Ex vivo gene delivery for stem cells of clinical interests using synthetic processes of cellular and nuclear import and targeted chromosomal integration 138 MOLEDA Molecular optimisation of laser/electrotransfer DNA administration into muscle and skin for gene therapy 141 ANGIOSKIN DNA electrotransfer of plasmids coding for an- tiangiogenic factors as a proof of principle of non-viral gene therapy for the treatment of skin disease 144 New Therapies – Table of contents 7 NEW THERAPIES TABLE OF CONTENTS Immunotherapy AND Transplantation 153 Allostem MimoVax The development of immunotherapeutic strate- Alzheimer’s disease-treatment targeting trun- gies to treat haematological and neoplastic dis- cated Aß40/42 by active immunisation 193 eases on the basis of optimised allogeneic stem cell transplantation 155 Pharma-Planta Recombinant pharmaceuticals from plants for DC-THERA human health 196 Dendritic cells for novel immmunotherapies 159 SAGE SME-led antibody glyco-engineering 200 DC-VACC Dendritic cells as natural adjuvants for novel vac- BMC cine technologies 165 Bispecific monoclonal antibody technology concept 202 THERAVAC Optimised delivery systems for vaccines targeted AUTOCURE to dendritic cells 169 Curing autoimmune disease. A translational ap- proach to autoimmune diseases in the post-ge- DENDRITOPHAGES nomic era using inflammatory arthritis and my- Therapeutic cancer vaccines 173 ositis as prototypes and learning examples 204 Genomes To Vaccines INNOCHEM Translating genome and proteome information Innovative chemokine-based therapeutic strate- into immune recognition 177 gies for autoimmunity and chronic inflammation 209 COMPUVAC Ration design and standardised evaluation of CELLAID novel genetic vaccines. 181 European symposia for the evaluation of poten- tials and perspectives of curative cell therapies HEPACIVAC for autoimmune diseases 214 New preventative and therapeutic Hepatits C vaccines: from preclinical to phase I 186 STEMDIAGNOSTICS The development of new diagnostic tests, new BacAbs tools and non-invasive methods for the preven- Assessment of structural requirements in com- tion, early diagnosis and monitoring for haemat- plement-mediated bactericidal events: towards a opoietic stem cell transplantation 217 global approach to the selection of new vaccine candidates 189 RISET Reprogramming the immune system for the es- tablishment of tolerance 221 8 New Therapies – Table of contents NEW THERAPIES XENOME Engineering of the porcine genome for xenotransplantation studies in primates: a step towards clinical application 224 CLINT Facilitating international prospective clinical trials in stem cell transplantation 228 TRIE Transplantation research integration across Europe 230 INDEX OF PROJECTS 233 INDEX OF COORDINATORS 234 New Therapies – Table of contents 9 10 NEW THERAPIES INTRODUCTION ew therapies” as used in the title here factors and transplantation science. Projects refers to treatments such as gene and described here focus on regeneration of tissues “Ncell therapy, immunotherapy, tissue such as bone and cartilage, skin, muscle, heart, engineering and regenerative medicine which pancreas and nervous tissue, through the use of offer hope for therapy of diseases which are cur- haematopoietic, mesenchymal, cord blood, hu- rently untreatable, where life is at stake, and for man embryonic and adult stem cells. In many cas- regenerating diseased, damaged or defective es projects take a comparative approach to iden- tissues and organs. Their main characteristic is tify the best sources of cells and to see how they that they employ large biomolecules, genes, perform in different tissues. Such comparisons cells and tissues as therapy rather than drugs or can also reveal insights into underlying knowl- pharmaceuticals. By addressing such conditions edge of the biological processes involved. High- as arthritis, diabetes, heart and neurodegenera- lights of the research include using stem cells to tive disease, new therapies address problems of reverse muscular dystrophy in a dog model of an ageing population, and as high-value, new the disease, and developing a technique to grow technologies, they represent an opportunity for pure brain stem cells. developing industrial competitiveness. GENE THERAPY. Gene therapy is the insertion The purpose of this compilation of information of genes into an individual’s cells and tissues to on EU-sponsored research in new therapies is treat a disease; its success depends on isolation to demonstrate the range of activities under- of effective therapeutic genes and on finding taken in this field during the course of the EU’s suitable vectors to deliver them into the patient’s Sixth Framework Programme for Research (2002- cells. The main approaches for gene delivery are 2006), notably under the heading “Applications viral, which often displays a high
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