Gene therapy restores immunity in severe congenital pathology

Researchers at the National Institute of Allergy and Infectious Diseases of the USA have developed a method of gene therapy that allows to safely update the immune system of children and young adults with the X-linked form of severe combined immunodeficiency (TCID-X1) – a severe hereditary disease that mainly affects male infants.

This form of hereditary immunodeficiency is caused by mutations of the IL2RG gene that disrupt the normal development and functioning of immune cells. Carriers of such mutations suffer from an extremely high predisposition to the development of life-threatening infectious diseases. To date, the only effective method of treating TKID-X1 is hematopoietic stem cell transplantation, ideally from an immunocompatible donor-sibling (sibling). Patients who do not have a suitable donor among siblings usually undergo stem cell transplantation from one of their parents, but this allows them to restore immunity only partially. Such patients need continuous therapy throughout their lives and may experience complex medical problems, including chronic infectious diseases.

As part of their study, the authors tested the safety and effectiveness of gene therapy used in combination with low-dose chemotherapy. In total, 5 patients aged 7 to 24 years old, suffering from progressively deteriorating functioning of the immune system, despite having previously undergone transplantation of hematopoietic stem cells from their parents, took part in the study.

Bone marrow cell samples were isolated from all patients, which were genetically modified using a lentiviral vector to introduce a normal version of the IL2RG gene. The cells modified in this way were injected back into patients after preliminary exposure to a low dose of the chemotherapy drug busulfan, the purpose of which was to facilitate the engraftment of therapeutic cells and the launch of the production of new blood cells.

The first two participants of the study had a significant increase in the effectiveness of immunity and an improvement in clinical status. The condition of one of them continues to improve 3 years after the procedure, while the second died 2 years after treatment due to pre-existing lung damage caused by infection. This indicates the exceptional importance of early intervention carried out before the development of irreversible organ damage. The remaining three patients underwent therapy 3-6 months ago and are beginning to show improvement in immune function. All surviving patients are under regular medical supervision.

Report by De Ravin et al. Lentiviral hematopoietic stem cell gene therapy for older patients with X-linked severe combined immunodeficiency is presented at the 57th Annual Congress of the American Society of Hematology, held December 5-8, 2015 in Orlando, Florida.

Evgeniya Ryabtseva

Portal "Eternal youth" http://vechnayamolodost.ru Based on NIH/National Institute of Allergy and Infectious Diseases: Gene Therapy Restores Immunity in Children and Young Adults with Rare Immunodeficiency.