Die Langzeitergebnisse einer Gentherapie bei der angeborenen Immunschwächekrankheit SCID sind ausgezeichnet, wenn die Ursache ein Adenosin-Deaminase-Mangel ist. Im Gegensatz zur X-chromosomalen SCID, wo es zu mehreren Todesfällen kam, leben alle zehn Patienten, wie ein Bericht im New England Journal of Medicine (2009; 360:447-458) zeigt.
SCID (für severe combined immunodeficiency) ist eine Sammelbezeichnung für eine Reihe angeborener Erkrankungen mit einem schweren kombinierten Immundefekt, der unbehandelt in der Regel rasch tödlich endet.
Die beste Therapie besteht in einer hämatopoetischen Stammzelltransplantation, die aber nur dann eine sichere Heilungschance bietet, wenn der Spender, in der Regel ein Geschwisterkind, HLA-identisch ist.
Wesentlich riskanter ist die Spende von einem HLA-fremden Spender, die wegen der starken Abstoßungsreaktionen oder einem Fehlschlagen des Transplantates can lead to death. For these patients, gene therapy was devised in the SCID "technically" is easy to perform.
must only stem cells from bone marrow donated by viruses and are equipped with a correct version of the defective gene. This therapy was at the end of the last decade advanced that the first patients were treated.
On Hôpital Necker in Paris were gentherapiert since 2000 children with X-linked SCID. The study was stopped three years later, when several children were suffering from leukemia. With them had imported by the virus gene in the wrong place inserted into the genome.
The "promoter" should stimulate the production of the new gene, suggested the formation of adjacent proto-oncogenes. The likelihood of such insertional oncogenesis was not small: 5 of the 20 previously treated children developed 2 to 5 years after gene therapy a lymphoproliferative syndrome, in which one of them died.
Nevertheless Editorialist Donald Kohn advised the University of Los Angeles and Fabio Candotti by the U.S. National Human Genome Research Institute in Bethesda, Maryland to look at the situation soberly (NEJM 2009, 360: 518-521). Not just because for many children affected with stem cell transplantation (if no suitable HLA-identical donor is available) at least as as risky as gene therapy.
The second reason for optimism is the fact that the long-term results are favorable to a further variant of SCID and have not been overshadowed by cancer.
All ten children between 2000 and 2006 by an Israeli-Italian working group led by Mary Grazie Roncarolo San Raffaele Telethon Institute were from Gene Therapy for deals in Milan, have survived. In nine children, gene therapy has restored the immune system, eight do not require further therapy (2009, 360: 447-458).
was with the children on a defective gene for the enzyme adenosine deaminase. It is the accumulation of toxic metabolic waste and to SCID, which is curable as in the X-SCID only for the lucky children who have an HLA-identical donor. Treatment with bovine adenosine deaminase is rarely satisfactory.
Why in the SCID due to adenosine deaminase deficiency have never came to leukemia is not clear, particularly as the methods for gene transfer were very similar. The results are a motivation for continued therapy.
The Editorialist provide equal opportunities in front of six currently under investigation in order to prevent built-in fuses that the promoters as advised in the patients in Paris out of control. ©
heat / www.aerzteblatt.de
abstract of the study
San Raffaele Foundation
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