A new study confirms the interest of gene therapy, a technique that uses a viral vector to replace deficient genes on the chromosomes of patients. In beta thalassemia, anemia linked to a deficient gene that causes the formation of an abnormal protein. Genetic therapy is now well under control and works in other diseases.
Some severe blood diseases are linked to deficiencies in certain genes on the chromosomes, and patients have no other option than repeated blood transfusions, with possible long-term intolerance, or bone marrow transplants. related donors.
This is the case with certain thalassemias including beta-thalassemia where there is a deficiency in the gene responsible for the secretion of β-globin (βA-T87Q), a protein essential for the composition of hemoglobin. A new study published in the New England Journal of Medicine shows that the β-globin deficient gene can be replaced by a transplant of a new gene into the stem cells of the marrow.
A success of the genetic transplant
In a study carried out on 13 patients, a genetic transplant, using a viral vector of the lentivirus type, succeeds in replacing the deficient gene in the stem cells of the marrow: this makes it possible to secrete enough red blood cells to be able to stop all transfusions at 12 of 13 patients.
The levels of hemoglobin synthesized by this new gene range from 3.4 to 10.0 grams per deciliters and the levels of total hemoglobin range from 8.2 to 13.7 grams per deciliters, which is normal levels. or close to normal.
New Quick Take video: Treating Severe β-Thalassemia https://t.co/a2903TdhWw pic.twitter.com/4sdC4zyoXN
– NEJM (@NEJM) April 18, 2018
Lentivirus is more reliable and safer than retrovirus
The technique of replacing the deficient gene via the “transducer lentivirus” confirms its effectiveness in this disease: it is a technique of grafting (“transfection”) of a gene on the DNA of the stem cells of the marrow which uses a lentivirus rather than a retrovirus.
This virus just serves as a transfector of the patient’s stem cells and is not transmissible. It is only responsible for carrying a functional gene in thalassemia, but also in other diseases, and does not expose to any risk.
Study finds that LentiGlobin gene therapy may reduce or eliminate the need for chronic red-cell transfusions for patients with transfusion-dependent β-thalassemia. Read the full study: https://t.co/5z2IdlJiad pic.twitter.com/R3JS9dAtQO
– NEJM (@NEJM) April 18, 2018
Robust and durable transfection
Stem cells with the defective gene are taken 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 mastered. It does not trigger any particular reaction and no abnormal clonal proliferation has been observed, nor any gene that could cause cancer.
Gene therapy also works in hemophilia
In study on hemophilia A in adults this time, a single infusion of an experimental genetic treatment results in greatly improved levels of Factor VIII, the blood clotting protein, which is no longer made in the blood. hemophilia A, due to the alteration of the gene. Eleven out of 13 adults achieved normal or near normal levels of Factor VIII up to 19 months of follow-up.
This is the first successful gene therapy trial in hemophilia A. Although several gene therapies have been shown to be 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 more complex gene.
Unlike the multiple intravenous infusions per week of the usual treatment, this gene therapy appears to have lasting effects with a single infusion.
.
