A world first: two children saved by gene therapy

JPEG Research conducted in France in the field of gene therapy, in collaboration with a German team, has just resulted in an original clinical trial. The collaboration of an international group of researchers has allowed the progression of a very serious brain disorder in two young boys to be checked through the use of a totally new gene therapy technique. A success that opens up significant prospects for the treatment of many diseases.

For the first time, a brain disease has been treated effectively by gene therapy. The results of this therapeutic trial, published in the prestigious journal Science, have had a considerable impact in France and in the United States. This major scientific advance also received extensive publicity during the Telethon held on 4 and 5 December in France as part of the annual campaign to raise funds for research into genetic disorders.

Adrenoleukodystrophy (ALD) is a dreadful genetic disorder that affects one in 20,000 boys and leads, in its most serious but also most frequent form, to a breakdown of the myelin sheath of the brain through which messages are sent and received. These lesions can rapidly affect the vital functions and bring about the death of the sufferer. It was as a result of seeing children suffering from ALD in his paediatric neurology department at the Saint-Vincent-de-Paul hospital in Paris, that Professor Patrick Aubourg began his research: on developing a biochemical marker for diagnosis and treatment by bone marrow allograft, with his colleague Pierre Bougnères, as well as the paediatricians and researchers in immunology Claude Griscelli and Alain Fisher of the Necker Hospital for Sick Children. “These grafts enable us to arrest the development of brain disorders, but only after a waiting period of several months,” stresses Patrick Aubourg. “Moreover they are still dependent on finding compatible donors and can lead to complications that are often fatal”.

The new approach consists of grafting the patient’s own bone marrow cells, after treatment by gene therapy. The sample stem cells collected are corrected using a medicinal vector derived from the AIDS virus. “An offshoot of research on AIDS, this discovery will have consequences for the treatment of patients suffering from this disease,” observes Patrick Aubourg in passing. After treatment, the stem cells are then re-injected. They then reach the bone marrow and head towards the brain where they play a corrective role. This process, though it might appear simple, is the culmination of many years’ work. The clinical trials were conducted by INSERM, the French National Institute for Health and Medical Research, the Assistance Publique-Hôpitaux de Paris (city of Paris public hospital system), and the Paris-Descartes University of Medicine.

The innovative analysis of the development of corrected cells, carried out by the team led by Christof Van Kalle (Deutsches Krebsforschungszentrum, Heidelberg, Germany), was also a deciding factor. “Alhough we must remain cautious, this analysis shows that there is no particular reason to fear any harmful effect related to the insertion of the vector,” points out Nathalie Cartier, director of research at INSERM, who coordinated all the work. After numerous tests, two trials were conducted in 2006, on two boys then aged 7: “more than three years later for the first child and two and a half years for the second, no worrying consequence was found,” comments Patrick Aubourg. “A third patient has been treated but it is still too soon to draw any conclusions.”

The scientists have managed up till now to correct some 15% of bone marrow stem cells and hope one day to correct 30% or even 60% of them, which would further shorten the time during which the disease continues to progress. Researchers and practitioners however stress the fact that the treatment stops the development of the disease, but does not cure it, hence the importance of early detection in high-risk families. A screening system at birth is also in the process of being validated in the United States.

Nathalie Cartier and Patrick Aubourg today envisage extending the clinical trials to other patients, in France and elsewhere. This major scientific advance is opening up new prospects by promoting the use of gene therapy vectors in the treatment of other diseases, such as thalassemia, a form of hereditary anaemia, or sickle cell anaemia, responsible for an anomaly in haemoglobin. Millions of people worldwide will no doubt eventually benefit from these cutting-edge treatments.

Sylvie Thomas
Photo:Bone marrow stem cells of one of the patients after treatment. The red areas show the presence of the corrected protein.
© Patrick Aubourg

Dernière modification : 23/12/2009

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