Blood disease gene therapy with side effects

Blood disease: Successful gene therapy - treatment with side effects.

(16.09.2010) With the help of gene therapy, the blood disease beta-thalassemia was successfully treated in a young man for the first time. However, unexpected side effects occurred that make the future use of the method questionable.

Beta-thalassemia is caused by a genetic defect and leads to red blood cell disease or to the lack of formation and too rapid degradation of hemoglobin. The result: anemia. As a hereditary disease, beta-thalassemia is widespread, especially in the Mediterranean region, where it is relatively common. Not only is the aetiology mentioned above characteristic of a disease, but most patients have an enlarged spleen and liver just a few months after birth. In addition there are growth disorders, severe damage to internal organs and bone malformations. Those affected can often not survive without blood transfusions unless they find a donor for the transplantation of blood stem cells from the bone marrow. However, blood transfusions are not only uncomfortable for the patients, they also have a negative impact on their health. Thus, a therapy-related iron overload in the course of life-long blood transfusions is extremely likely, with severe organ damage in the heart, liver and pancreas may be the result of such iron poisoning.

Therefore, the news of successful gene therapy for all those affected a glimmer of hope, which was significantly clouded by the serious side effects. So is the one in the British science magazine „Nature“ Although the young man described seems to have been successful in gene therapy, there has been an uncontrolled growth of blood stem cells that, according to the researchers, may also be a precursor to blood cancer. The patient was treated with genetically modified, endogenous cells in 2007 at the age of 18. The physicians at Harvard University (Boston, USA) used genetic engineering for lentiviruses, which were used as gene shuttles in the cells. Since 2008, the patient, according to Philippe Leboulch from Harvard University, no longer had to receive a blood transfusion. In gene therapy, however, there was a potential side effect, which, according to the experts, needs to be further investigated and may be malignant. Apparently, the use of lentiviruses as gene shuttles changed the activity of a gene (HMGA2), which controlled the behavior of blood stem cells and stimulated them after therapy to uncontrolled growth. Although so far only benign cells are distributed in the patient, this could, according to Philippe Leboulch but also represent a precursor of blood cancer. For example, further studies are needed to investigate which forms of uncontrolled cell growth are taking place and what treatment success can be achieved in other patients using the method. In any case, gene therapy has helped the described patient in the short term. Since the age of three, he has received blood transfusions and the spleen had been removed at the age of six. (Fp)