X-linked chronic granulomatous disease (X-CGD) is a rare genetic disorder, which affects boys. It is a primary immunodeficiency disorder which results from an inability of the white blood cells called phagocytic cells (or phagocytes) to kill invading bacteria and fungi. These cells have difficulty forming the free radicals (most importantly the superoxide radical due to defective phagocyte NADPH oxidase complex) which are important in the killing of ingested pathogens. In X-CGD (which accounts for two thirds of CGD patients), the defect lies in a gene which makes up a critical part of the NADPH-oxidase complex (the catalytic subunit; gp91-phox protein). 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
Transplantation of patient's autologous CD34+ cells transduced with lentiviral vector containing XCGD gene. The investigational product is patient-specific and corresponds to autologous CD34+ cells transduced ex vivo with the G1XCGD vector. These transduced cells will be cryopreserved until safety testing and infusion into the patient.
Hôpital Necker Enfants Malades
Paris, France
Safety as measured by the incidence of adverse events
Time frame: 60 months
Restoration and stability over time of the NADPH functioning granulocytes assessed by a Dihydrorhodamine (DHR) flow cytometry test
Time frame: 12 months
Clinical improvement
Assessed by: complete physical examination to assess the normalisation of nutritional status, the growth, the development, the decrease in the severity of the infection and/or inflammatory complication at inclusion.
Time frame: 60 months
Percentage of transduced CD34+ haematopoietic cells infused and of blood cells over time
Time frame: 60 months
Immunological reconstitution
Assessed by: evidence of restored neutrophil functionality (DRH test), expression of gp91phox protein by flow cytometry and immunity against bacterial and fungal infections over time.
Time frame: 60 months
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