Prenatal Gene Therapy for Genetic Diseases - Hopes, Fears and Ethical Considerations

Abstract

[evdate 2012-03-09] IAS Distinguished Lecture. 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 Prof Coutelle 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.

Prof Charles Coutelle, MD, DSc, is Emeritus Professor of Gene Therapy at the National Heart and Lung Institute (NIHL), Imperial College London. He 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.

Duration: 92 min.