A new victory for gene therapy
Maxim Rousseau, Polit.<url>, based on MedPage Today: Breakthrough: Gene Therapy Effective for Young Sickle Cell Patient
French scientists have reported the first ever successful use of gene therapy to cure sickle cell anemia.
About 300 thousand children with sickle cell anemia are born every year in the world. This disease is caused by a mutation in the gene encoding one of the subparticles of the hemoglobin molecule. It leads to a change in the shape of a protein molecule in red blood cells (instead of hemoglobin A, hemoglobin S appears). Erythrocytes with defective hemoglobin have a characteristic crescent shape, whereas normal erythrocytes have the shape of a disk with a concave core.
Sickle-shaped red blood cells are destroyed more often than usual, which leads to permanent anemia, since due to the death of red blood cells, tissues do not receive oxygen. In addition, such red blood cells are less plastic and less able to pass through narrow capillaries. Frequent blockage of capillaries in patients leads to various disorders, the appearance of thrombosis in the liver and spleen, arthritis, ulcers on the legs, besides, anemia and constant fatigue are always characteristic of them. In some cases, blockage of the retinal capillaries can lead to blindness. The only form of non-palliative treatment for such patients until recently was a donor bone marrow transplant, but not all of them manage to find a suitable donor, besides transplantation requires lifelong use of drugs that reduce immunity.
The new method was first successfully tested on animals, and in 2014, the first human clinical trial was launched at the Necker Children's Hospital in Paris. Scientists worked with a thirteen-year-old boy with a severe form of sickle cell anemia. Due to the consequences of the disease, he developed bilateral osteonecrosis of the hip joint, he also underwent removal of the spleen and gallbladder. The researchers took a sample of the boy's bone marrow tissue. Multipotent hematopoietic cells were isolated from the tissue. With the help of a specially designed virus, they introduced genes of another form of hemoglobin into its cells. Moreover, they used not just the hemoglobin A gene, but achieved the replacement of one amino acid in the molecule of this protein (glutamine for threonine). This variant of the gene was found in some children who were expected to have sickle cell anemia, but its symptoms did not manifest.
After that, the scientists used the drug busulfan to destroy the remaining hematopoietic cells in the boy's body. This procedure is usually done before a bone marrow transplant. Then the boy was returned the cells taken from him with the now modified gene responsible for hemoglobin.
About six months after the procedure, the hemoglobin level in the boy's blood reached 106 – 120 grams per liter (with a norm for his age of 110 – 160 grams per liter). Partly it was hemoglobin S, partly it was normal hemoglobin A. After nine months, normal hemoglobin was 46% of the total hemoglobin in the body, and 15 months after the transplant, the normal hemoglobin was already 48%. This amount of hemoglobin A is enough to make the symptoms of sickle cell anemia disappear. During all 15 months, the patient had no manifestations of the disease. And doctors were able to cancel additional therapy with medications and blood transfusions. In the future, the researchers will only monitor the condition of the boy's blood to find out whether the normal version of hemoglobin in his body will continue. In the meantime, we can say that the boy, who had been suffering from a serious illness for many years, got rid of it.
Currently, clinical trials of a similar treatment method are taking place with the participation of a number of patients with sickle cell anemia and beta-thalassemia (more information about this disease and the use of gene therapy for its treatment can be found in a special essay). Messages about their results are expected.
The results of the study were published New England Journal of Medicine (Ribeil et al., Gene Therapy in a Patient with Sickle Cell Disease).
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07.03.2017