Friday, 14 Dec 2018

Gene therapy radically improves the beta-thalassemia, a severe genetic anemia

Some severe blood diseases are linked to certain deficiencies, on chromosomes and patients have no option but repeated blood transfusions, with possible long-term intolerance, or related bone marrow transplants .

This is the case with certain thalassemias including beta-thalassemia where there is a deficiency of the β-globin gene (βA-T87Q). A new study published in the New England Journal of Medicine shows that the deficient gene can be replaced by a lentivirus-based transplant to penetrate the deficient cells of the marrow.

A successful genetic transplant

In a study of 13 patients, a genetic transplant, using a lentivirus viral vector, replaces the deficient gene in the marrow stem cells to secrete enough red blood cells to stop all transfusions. in 12 of the 13 patients. The hemoglobin levels synthesized by this new gene range from 3.4 to 10.0 grams per deciliter and the total hemoglobin levels range from 8.2 to 13.7 grams per deciliter, which is normal levels. or close to normal.

Lentivirus is more reliable and safe than retrovirus

The technique of replacement of the deficient gene via a “transducing lentivirus” confirms its effectiveness in this disease: it is a technique of transplantation (“transfection”) of a gene on the DNA of the stem cells of the marrow. uses a lentivirus rather than a retrovirus.

This virus serves as a transfector of the patient’s stem cells and is not transmissible. It is responsible for conveying a functional gene in thalassemia, but also in other diseases.

Robust and durable transfection

Stem cells with the deficient gene are removed from the patient. They are then “transfected” by the lentivirus, that is to say the functional gene is integrated into their genetic material, their chromosomes, then these cells are reinjected into the patient. The process is well controlled. It does not trigger any particular reaction and no abnormal clonal proliferation was observed, as well as no gene that could cause cancer.

Gene therapy also works in hemophilia

In study on adult hemophilia A this time, a single infusion of experimental gene therapy provides significantly improved levels of Factor VIII, the blood coagulation protein, which is no longer manufactured in Canada. hemophilia A, because of the alteration of the gene. Eleven out of 13 adults achieved normal or near normal levels of Factor VIII and this up to 19 months of follow-up.
This is the first successful gene therapy trial in hemophilia A. Although several gene therapies have proven effective in hemophilia B, a rarer form, gene therapy for hemophilia A is considered more difficult because it is associated with a much larger and complex gene.

Unlike multiple intravenous infusions per week of usual treatment, this gene therapy appears to have lasting effects with a single infusion.

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