Gene Therapy for X-linked Chronic Granulomatous Disease (X-CGD) (CGD)

A Phase I/II, Non Randomized, Multicenter, Open-label Study of Autologous CD34+ Cells Transduced With the G1XCGD Lentiviral Vector in Patients With X-linked Chronic Granulomatous Disease

X-linked chronic granulomatous disease (X-CGD) is a rare genetic disorder, which affects boys. It is caused by an error in a gene that makes part of the immune system. The basic defect lies in specialised white blood cells called phagocytic cells (or phagocytes), which are responsible for protection against infection by destroying invading bacteria and fungi. They do this by pouring large amounts of substances similar to bleach onto these organisms. In CGD, there is a defect in the system that makes the bleach, called the NADPH-oxidase. In X-CGD (which accounts for two thirds of patients), the defect lies in a gene which makes up a critical part of the NADPH-oxidase (known as gp91-phox), and the cells cannot make bleach-like substances. Therefore they kill bacteria and fungi poorly, and the patients suffer from severe and recurrent infections. This also results in inflammation which can damage parts of the body such as the lung and gut. In many cases, patients can be adequately protected from infection by constant intake of antibiotics. However, in others, severe life-threatening infections break through. In some cases, inflammation in the bowel or urinary systems results in blockages which cannot be treated with antibiotics, and which may require the use of other drugs such as steroids. Development of curative treatments for CGD is therefore of great importance.

Transplantation of patient's autologous CD34+ cells transduced with lentiviral vector containing GP91PHOX gene

Normalisation of nutritional status, growth, development, severe infection and/or inflammatory complication which recommended patient's inclusion

Inclusion Criteria: Male X-CGD patients Molecular diagnosis confirmed by DNA sequencing At least one prior ongoing or resistant severe infection and/or inflammatory complications requiring hospitalisation despite conventional therapy No HLA-matched donor available after 3 months search unless the risk of waiting for a potential match or for performing an allogeneic transplant is considered unacceptable by the investigator Exclusion Criteria: Contraindication for leukapheresis Contraindication for administration of conditioning medication Administration of gammainterferon within 30 days before the infusion of transduced autologous CD34+ cells

Department of Hematology/Oncology, University Hospital Frankfurt and Institute for Biomedical Research, Georg-Speyer-Haus, Frankfurt - Germany