This disease is characterized by severe and recurrent sometimes lethal infections which begin in the first months of life, associated with diarrhea and growth retardation. The infections may be viral, bacterial of fungal. Vaccination with BCG may lead to disseminated infection.
The disease mainly affects boys who die by the age of one if they are not treated. The study of their immune system reveals lymphopenia with absence of T lymphocytes and NK cells, whereas B lymphocytes are present in normal or increased numbers.
The disease is due to an abnormality in the IL2RG gene, which encodes the gamma chain common to several interleukin receptors that are growth factors for lymphocytes. The incidence of the disease is 1/200,000 births.
For patients with no compatible bone marrow donor, gene therapy based on correction of autologous HSC represents a major hope.
Genethon has developed a safe lentiviral vector to express an optimized form of the IL2RG gene in stem cells and the immune system of patients.
This project is being conducted within the framework of a European consortium (SCIDNET).
Poletti, V. et al. (2018). “Preclinical Development of a Lentiviral Vectore fo Gene Therapy of X-Linked Severe Combined Immunodeficiency” Mol Ther methods Clin Dev 9:257-269.