Abstract
Genetic diseases can affect everyone. Often they occur without previous indication of such condition in the affected family and they are frequently manifesting early in life with devastating consequences and little means of therapeutic intervention. Gene therapy offers, in principle, a curative therapy for such disease by application of the normal gene to a patient in order to compensate for the gene defect causing such disease. However, in many cases postnatal gene therapy may not be effective for various reasons.
Prenatal (fetal or in utero) somatic gene therapy may allow treating genetic diseases before significant organ damage has occurred. It may provide long-term curative effects by gene delivery to still expanding stem cell populations and by conferring postnatal immune-tolerance against the therapeutic transgenic proteins and vectors. Over more than 15 years the speaker and his research group have investigated different vector systems and animal models to develop means of effective gene delivery to all relevant fetal organ systems and to demonstrate proof of principle for a curative effect of in utero gene application on mouse models of genetic diseases. They have also extended these studies to sheep and primates, which allow the application of techniques applied in human fetal medicine for the delivery of our therapeutic gene constructs.
These investigations have confirmed the predicted advantages of prenatal gene therapy. They have, however, also raised new questions concerning possible side effects of this approach such as the consequences of inadvertent germ-line gene transfer and the risks of developmental aberrations or oncogenesis.
Scientific as well as ethical considerations concerning the improvement of vector safety, the choice of diseases, the development of in utero monitoring procedures and safeguarding adequate information and freedom in patient consent and decision making, are now central aspects of long-term studies in preparation for a potential human application.
About the speaker
Prof Charles Coutelle, MD, DSc, is Emeritus Professor of Gene Therapy at the National Heart and Lung Institute (NIHL), Imperial College London. He studied Medicine at the Friedrich-Schiller-University, Jena, Germany and received his MD in 1963. After several years of clinical work at the Charité Hospital, Humboldt University Berlin, he took up a postgraduate training in Biochemistry at the Institute for Biochemistry and was awarded the degree of DSc in this field in 1974. In 1973 he moved to the Central Institute of Molecular Biology of the Academy of Sciences of the GDR in Berlin-Buch, where he became Professor in 1981 and worked as Head of the Department of Molecular Human Genetics on problems of gene expression, human gene mapping and DNA diagnostic of human genetic disease.
In 1992 he accepted the position of director of the newly founded Cystic Fibrosis Gene Therapy Group at St Mary's Hospital, London, which conducted the first clinical gene therapy trial for cystic fibrosis with non-viral vectors in collaboration with two other British groups. Following this study, he turned with his Gene Therapy Research Group at Imperial College to more fundamental questions of the development of viral and non-viral vector systems for gene therapy and animal models for gene therapy of genetic diseases (cystic fibrosis, DMD, haemophilia). In the last 15 years of his career he led several projects to study prenatal gene therapy as an approach towards prevention of severe early-manifesting human genetic disorders.
Prof Coutelle retired in 2008 but remains associated with Dr Richard Harbottle’s Gene Therapy Research Group at NIHL. His main interest remains gene therapy for human genetic disease with particular emphasis on prenatal gene therapy and novel vector systems.
He is a founding member of the British Society for Gene Therapy and the American Society of Gene and Cell Therapy and is Fellow of the Leibnitz Society Berlin.
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