Friday, 14 Dec 2018

The spectacular effectiveness of gene therapy against beta-thalassemia, serious genetic disease

A new method of genetical therapy has allowed patients with a rare rare disease, beta-thalassemia, to dispense partially or totally from regular blood transfusions previously necessary for their survival. These first results concerning 22 patients of an international study are the object of a publication Wednesday, April 18, 2018 in the prestigious journal New England Journal of Medicine . This work is to be attributed to the Parisian research institute Imagine and Necker Hospital (Public Assistance-Hospitals of Paris), in collaboration with an American biotech company, bluebird bio.

Beta-thalassemia, a genetic disease of red blood cells that requires regular transfusions

Beta-thalassemia is one of the most common genetic diseases resulting from a defect in the gene allowing the production of hemoglobin, the oxygen-carrying protein in red blood cells. Thalassemias conferring protection against the parasite of malaria, they are frequent in the regions affected by this infectious disease (Middle East, Asia, Sub-Saharan Africa, Mediterranean rim in Europe). Rare in the serious form of pathology, there are around 100,000 patients in the world and 350 in France. according to Orphanet . Beta-thalassemias are in fact of variable severity depending on whether the mutation decreases or completely cancels out the production of hemoglobin. ” In the most serious form, one is totally anemic, and dependent on a monthly blood transfusion for life Philippe Leboulch, founder of bluebird, told AFP that some light forms cause no symptoms when other very severe are lethal if they are not treated.The only treatments today are allografts healthy bone marrow by a compatible donor, but most patients undergo regular transfusions, requiring them to take iron chelating treatments to fight its accumulation, toxic to the body.

The advent of gene therapy was done in 2010 on a single patient

It was in 2010 that the researcher and professor Marina Cavazzana, also at the origin of the works of 2018, publishes the case of a severe beta-thalassemic patient who, thanks to the use of gene therapy, has since been able to do without her transfusions. The method is simple: we first take the patient’s own stem cells from the patient’s bone marrow, which is corrected in the laboratory using a so-called “vector”, and which is actually a modified virus for which it does not insert its viral DNA, but a selected DNA (here the genes necessary for the production of functional hemoglobin). Although it is not the CRISPR technology that is much talked about in recent years, the principle of this vector is the same. The patient then undergoes treatment to remove his diseased bone marrow, and is then reinjected his own cells modified by the vector. ” We add gene, to replace the missing one, thanks to a sort of Trojan horse that will bring therapeutic DNA “, says Professor Leboulch.This is to test the effectiveness and tolerance of a similar vector, called LentiGlobin and produced by bluebird bio, that these new works on a larger scale were made in France and the United States of 22 beta-thalassemic patients.

3 years after treatment, 15 out of 22 patients no longer need transfusions

For Professor Cavazzana, the results are spectacular. Among these patients, ” none is complicating. There are no side effects Thus, the 9 patients with the most severe form of the disease had their transfusion needs reduced by 73%, 3 of them having absolutely no need of it at all, and the other 13 patients With the most common form of beta-thalassemia and various variations, 12 of them no longer needed transfusions after treatment at the end of 3 years of follow-up over the 15 years minimum planned in total . ” These results are of great importance “, says the review New England Journal of Medicine in an editorial . “The results here come from (…) are incredibly promising Dr. Darren Griffin, a professor of genetics at the University of Kent, said on Science Media Center that he discovered these works, calling them ” significant advance “, especially for the” quality of life of patients “which is greatly improved by the interruption of blood transfusions.A 20-year-old patient treated in Paris, of Thai origin, has also testified of her” second life “.” The treatment was hard, in a sterile environment for two months. I could not eat by the mouth. It was very long not being able to go out “, she told AFP.” But now everything is normal in my health. I eat everything, I play sports, I study. Removing transfusions from my life has helped me a lot “.

With AFP

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