A gene therapy can protect CD4 cells from attack by the HIV virus and stabilize the immune system. The effects were evaluated in a randomized clinical study (Nature Medicine 2009; doi: 10.1038/nm.1932) but (still) too weak for a broader clinical application at the present time.
for gene therapy of the 74 HIV-infected participants of the study was first taken from bone marrow. This, the researchers isolated these CD34-positive cells as stem cells, precursors of CD4 cells. The CD34 cells were then in the laboratory - provided in some of the participants with an additional gene - with the help of a virus. For the other participants was a sham treatment.
The therapeutic gene contains the genetic information for the ribozyme OZ1. Ribozymes are molecular scissors that cut specific genes and thereby inactivate. In this case, destroyed OZ1 the tat gene of HIV virus, which is required for virus replication in CD4 cells.
after gene therapy (or sham treatment), the CD34-cells in HIV-infected individuals were re-infused. This is done in the hope that the resulting from them CD4 cells are resistant to HIV and maintain the integrity of the immune system remains.
This seems now to be successful in the first randomized study - albeit with significant compromises. In the first months hatte die Gentherapie keine Auswirkungen auf den Verlauf der HIV-Therapie, wie Ronald Mitsuyasu vom Aids Institute der Universität von Kalifornien in Los Angeles (UCLA) und Mitarbeiter berichten.
Die Konzentration der HI-Viren im Blut waren – gemessen an einer temporären Unterbrechung der antiretroviralen Therapie – nicht niedriger als im Placebo-Arm der Studie. Erst ab der 40. Woche zeichnete sich eine signifikante Abnahme der Viruslast ab.
Die Zahl der CD4-Zellen war im Gentherapie-Arm jedoch während der gesamten 100 Wochen der Studie höher als im Placebo-Arm (gegen Ende soll es dann zu einem Absinken der CD4-Zellen gekommen sein). Die Verträglichkeit wird als gut beschrieben. Spezifische Nebenwirkungen gene therapy will not have seen the group Mitsuyasu.
The results should therefore initially be only a starting point for further experiments. For clinical use, the effects were far too low. A replacement for the long-term anti-retroviral therapy is not gene therapy dar.
Research is expected in the direction of a combination go of gene therapy with a Knochenmarksablation, but this is risky and therefore ethically very questionable, as long as the patients come with anti-retroviral drugs to satisfactory therapeutic results . can heal
that a stem cell therapy for HIV infection, had Gero Hütter of the Berlin Charité - if in a different situation - show recently in a spectacular individual cases. A 40-year-old HIV patient had received due to a recurrent acute myeloid leukemia, an allogeneic stem cell therapy.
happened to be the donor carrier of a mutation in the CCR5 gene that makes the CD4 T cells resistant to HIV infection. The patient is now 20 months since virus-free and therefore in all probability of his HIV infection healed (NEJM 2009, 360: 692-698).
Because of the significant risks that stem cell therapy is currently not eligible. It should however be the starting point for further experiments, like Jay Levy of the University of Southern California in San Francisco in an editorial (NEJM 2009, 360: 724-725) executes. ©
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