Zusammenfassung
Zu den potenziellen Einsatzmöglichkeiten der Gentherapie hereditärer monogener Lebererkrankungen gehört neben der Hepatozyten- bzw. Stammzell- und Lebertransplantation, die spezifische Reparatur bzw. der gezielte Ersatz eines defekten Gens. Während die prinzipielle Wirksamkeit dieser Strategien zur Behandlung isolierter Gendefekte in vivo in experimentellen präklinischen Modellen bzw. in individuellen Patienten gezeigt werden konnte, ist der potenzielle Stellenwert der Gentherapie aktuell noch schwer zu beurteilen. Neben zahlreichen ungelösten methodischen Problemen des Gentransfers und der Kontrolle der Genexpression u.a.m. sind die Langzeiteffekte der Gentherapie in vivo schwer abschätzbar. Dennoch ist zu erwarten, dass zell- und gentherapeutische Strategien die Behandlung von Patienten mit hereditären monogenen Lebererkrankungen komplementieren oder ersetzen werden. Aktuelle Fortschritte auf dem Gebiet der Stammzellforschung mit der vor kurzem gelungenen Herstellung von patienteneigenen pluripotenten Stammzellen eröffnen sich darüber hinaus neue Perspektiven, die sich auch auf die weiteren Entwicklungen auf dem Gebiet der Gentherapie und besonders der Stammzelltransplantation auswirken werden.
Abstract
Gene therapy has been explored for the treatment of hereditary monogenic liver diseases. It includes gene repair, gene replacement as well as hepatocyte, stem cell or liver transplantation. These strategies have been successfully explored in preclinical in vivo models of hereditary monogenic liver diseases as well as in individual patients. While their principle and efficacy has been demonstrated, in principle, numerous problems need to be solved before gene therapy will complement or replace existing therapeutic options. Furthermore, recent developments in the field of stem cell biology with the generation of individual stem cells from skin fibroblasts will certainly also have an impact on further developments in gene therapy in general and stem cell transplantation in particular.
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Blum, H. Gentherapie von hereditären Lebererkrankungen. Gastroenterologe 3, 227–232 (2008). https://doi.org/10.1007/s11377-008-0179-9
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DOI: https://doi.org/10.1007/s11377-008-0179-9