Gene therapy for "children in a bubble"
New gene therapy restored immunity in children with rare immunodeficiency
Anatoly Glossev, Vesti
Children for whom any infection was deadly, got a chance for a normal life thanks to experimental treatment. A new method of gene therapy has restored the production of immune cells in the bone marrow, disrupted by a rare genetic disease – X-linked severe combined immunodeficiency (X-linked severe combined immunodeficiency, or X-SCID). At the same time, he did not show the dangerous side effects inherent in previous methods of combating this ailment.
The achievement is described in a scientific article published in the New England Journal of Medicine by a large international group of researchers (Mamcarz et al., Lentiviral Gene Therapy Combined with Low-Dose Busulfan in Infants with SCID-X1).
As the name implies, X-SCID is associated with a mutation in the X chromosome. Damage to the IL2RG gene leads to the fact that the patient does not produce enough of the most important immune cells: T-lymphocytes, B-lymphocytes and natural killers, they are also NK cells (from the English natural killers). As a result, any infection threatens his life. Usually such children die a year or two after birth if they do not receive treatment against X-SCID in time.
Currently, this ailment is treated with a bone marrow transplant. It is best if the donor is a brother or sister of the patient, but less than 20% of patients have this opportunity. The rest have to transplant cells that are less suitable for them. As a result, immunity is not fully restored, and the patient needs treatment all his life. In addition, the transplantation of someone else's bone marrow requires harmful chemotherapy in large doses so that the donor material is not rejected.
The idea of gene therapy is to correct a defective gene in the patient's own cells. Viruses are used for this.
It is known that viruses cannot reproduce on their own. Penetrating into the cell, such an invader "intercepts control" of the mechanisms of DNA synthesis and forces them to produce his own genetic copies. In gene therapy, the natural ability of viruses to manipulate other people's DNA copying systems is used to treat hereditary diseases.
The authors of the new study took hematopoietic bone marrow stem cells from patients and infected them with a specially created virus. The role of the latter was to replace the defective IL2RG gene with its normal variant. The "cured" cells were transplanted back to the patient.
Since the child received his own cells, they were practically not rejected. It took only a low dose of a chemotherapeutic drug for the cells to take root.
The study involved eight children aged two to 14 months. After the procedure, the researchers monitored their health for more than 16 months.
3-4 months after treatment, the number of B-lymphocytes and NK cells in all patients returned to normal, and seven out of eight subjects also had T-lymphocytes. The level of T-lymphocytes in the eighth child was normalized by repeated transplantation of "corrected" cells.
In addition, four children no longer needed injections of immunoglobulins, and three of these four developed a normal reaction to the vaccine against an infectious disease.
"These exciting new results show that gene therapy can be an effective treatment option for children with this extremely serious disease, especially for those who do not have an optimal donor for stem cell transplantation. This progress gives them hope for the development of a fully functional immune system and the opportunity to live a full healthy life," emphasizes Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health.
This study is not the first in which gene therapy is used against X-SCID. However, in previous experiments, it was possible to restore the normal level of only T-lymphocytes, but not B-lymphocytes and NK cells.
In addition, subjects in some early studies subsequently developed leukemia. This was most likely a side effect of the virus on the DNA of cells: it affected not only the gene for which it was intended. Biologists have created another virus, safer, for treatment using the new method.
At the time of publication, no serious side effects from the treatment were observed in the subjects. Surveillance of them continues. The authors are also going to try this treatment on other patients.
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