First successful gene therapy against the beta-thalassemia

After a difficult start, gene therapy would, at the forefront? A great victory has at least been announced by scientists. One young man with β-thalassemia, the most common genetic disease in the world, would have been cured by this technique.

In healthy people, mainly hemoglobin is present in red blood cells. It is a protein complex composed of two α chains and two β chains. On each, an iron atom that gives the red blood provides the setting and release oxygen. Hemoglobin is essential for transporting oxygen.

The β-thalassemia, also known as red cell disease is a hereditary form of anemia that affects 200,000 children each year at birth.Recessive disease is characterized by a mutation carried by the two parental chromosomes 11, resulting in the alteration of the β chain of hemoglobin. Under these conditions, the protein complex of hemoglobin is not formed correctly and the transport of oxygen is impaired.

From a clinical point of view, without treatment, the disease is often fatal before the age of 8 years. Regular blood transfusions are needed to overcome anemia, extensive treatment, not curative, but which extends the life expectancy considerably.

Like any genetic disease, only a modification of altered gene can be cured. Stem cell transplants have been successful, but the lack of suitable donors is a real obstacle to its expansion. A team of researchers, including Philippe Leboulch (CEA, Inserm, Harvard Medical School) have tried other methods such as gene therapy or the insertion of a gene drug in the patient's cells, a method that had proven itself mouse.

Hemoglobin is composed of two chains of the α-globin (red) and two chains of β-globin (blue). The iron atoms are at the center of the structures "heme" (green). © Wikimedia Commons

Reproducible therapy?

The project, published in the journal Nature, was conducted on a young man of 18 suffering from the disease and of course voluntary.This patient, suffering from β-thalassemia βE/β0, has a gene for the synthesis of β-globin gene unstable and nonfunctional.

There are now 3 years old, Marina Cavazzana-Calvo, University Paris Descartes, has collected stem cells from bone marrow that give rise to blood cells including red blood cells. These cells were cultured with a lentivirus vector type containing the healthy version of the gene for β-globin. Infection by the lentivirus, which resembles the AIDS virus, causes the insertion of the viral genome into the genome of the cell and with it the healthy gene.

The cells with the gene product were then reintroduced into the patient's bone marrow. Approximately one year after transplantation and with the constant increase in the rate of β-globin, transfusions became unnecessary. Despite a slight anemia residual life of the young man, now aged 21, has actually improved.

But this success is mixed: the HMGA2 protein linked to the development of certain cancers is overexpressed in some transplanted cells, probably because of the insertion site of the gene product. For researchers who have not participated in this event could both instigate healing by promoting cell survival, but also become a danger to the patient. They felt it would be a healing occurred due to fortunate circumstances and uncontrolled.

If gene therapy is far from being safe for the moment, a milestone has been reached, however. The significant increase in the rate of β-globin is a victory in itself and should lead to trials on a dozen other patients.