[Gene therapy in primary immunologic failure].

Abstract

BACKGROUND: Primary immunodeficiency diseases (PID) represent a group of rare, usually congenital diseases. In most cases they are caused by mutations in genes essential for normal function of the immune system, leading to severe deficiency in antimicrobial defences, in many cases associated with other clinical manifestations. During the last decade the genetic defect and the function of the normal gene in the immune system has been delineated for a number of PID. The diseases are usually serious, and curative therapy is not available unless allogeneic bone marrow transplantation is possible. PID is therefore considered an attractive goal for gene therapy. MATERIAL AND METHODS: A systematic survey was made of protocols for gene therapy available in major databases, as well as of published reports on trials with gene therapy in man. RESULTS: Clinical trials with gene therapy are ongoing in several types of PID. While no case of PID has been documented to be definitely cured with gene therapy up to now, a landmark finding was recently made, reporting the use of gene therapy to successfully treat two infants with a type of severe combined immunodeficiency (SCID). INTERPRETATION: Gene therapy holds considerable promise for treatment of several types of PID in the future. Important obstacles, which must be overcome, are partly associated with general problems in human gene therapy, partly with special difficulties associated with the complexity of the human immune system.