X-linked Chronic Septic Granulomatosis is a rare genetic disorder that affects mainly boys. It is caused by a mutation of the CYBB gene reducing the enzyme activity of NADPH oxidase in immune system cells, which prevents the destruction of microorganisms entering the body. Because of this deficiency, patients with Chronic Septic Granulomatosis are predisposed to infections caused by fungi and bacteria.
From the first years of life, XCGD patients suffer from repeated infections, sometimes deep abscesses, atypical pneumonias, but also from chronic inflammation, including in the gums or in the digestive tract.
The disease is severe and disabling, requiring constant treatment to limit infections with sometimes long hospitalizations, and life expectancy without treatment is 30 to 40 years.
Gene therapy based on correction of autologous HSC represents a major hope for a cure for patients who cannot benefit from a bone marrow transplant.
The gene therapy approach consists in expressing the CYBB gene in the phagocytic cells of the patient using a lentiviral vector. This lentiviral vector was developed by Genethon and collaborators.
Genethon obtained “Orphan Drug” status for this product from the European Medicines Agency (EMA).
Genethon is sponsoring two clinical trials for patients carrying mutations in the gene encoding gp91phox (about 75% of CGD patients).
Five patients have been treated out of the eight planned (it should be noted that some patients received treatment in the framework of a compassionate treatment program).
This international effort was supported by the European Commission by funding through the Net4CGD program which is a large-scale integrating project in Health Research of the European Commission 7th framework programme, coordinated by Genethon.
Genethon has signed a partnership agreement with Orchard Therapeutics for study data in the UK.
- Orchard Therapeutics and Généthon announce a gene therapy alliance in X-linked chronic granulomatous disease (15/12/2017)