Radiosensitive Severe Combined Immunodeficiency (SCID-X1)

Research Pre-clinical phase Phase I or I/II  

X-linked severe combined immunodeficiency (SCID-X or SCID X1) is characterized by severe and recurrent infections, sometimes lethal, 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 at about age one if they are not treated. A 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 which is common to several interleukin receptors, which are growth factors for lymphocytes. This disorder has an incidence of the order of 1/200,000 births. The only treatment possible for this severe immune deficit is a bone marrow graft, with all the risks associated with this procedure (graft vs host disease, immunosuppressive therapy).

For patients with no compatible bone marrow donor, gene therapy based on correction of autologous human stem cells represents a major hope.

Several gene therapy trials have already been carried out. Gene transfer into hematopoietic stem cells of the patient seem to represent a promising therapy for this disorder. However, some aspects of this treatment need to be improved, notably in order to obtain a correction of humoral immunity to enhance vector safety and to facilitate pharmaceutical development.

The Genethon project is to develop a secure lentiviral vector for expressing an optimized form of IL2RG gene in stem cells and immune system of patients.

This project is conducted in collaboration with teams including the Imagine Institute of the Necker Hôpital-Enfants Malades (Paris) and those of the Institute of Child Health (London).