Wiskott-Aldrich syndrome

Wiskott-Aldrich syndrome is a hereditary genetic disease of the immune system. It causes very varied reactions, from bleeding to autoimmune manifestations of eczema and tumors, and may become life-threatening. Genethon has conducted an international gene therapy clinical trial to treat this pathology.

What is Wiskott-Aldrich syndrome?

Wiskott-Aldrich syndrome is a complex, rare and severe immune deficiency of genetic origin, linked to the X-chromosome, and affecting an estimated 1/250,000 people. It is caused by mutations of the gene coding the WAS protein (WASp) expressed in the hematopoietic cells. This pathology, which affects mainly boys, leads to hemorrhage, severe repeated infections, severe eczema and, in some patients, auto-immune reactions and cancer. The only treatment currently available is bone marrow graft, which requires a compatible donor.

Wiskott-Aldrich syndrome: Genethon’s role

For patients without a compatible donor, gene therapy based on correction of autologous hematopoietic stem cells brings considerable hope.
Anne Galy’s team (Genethon/INSERM U951) has developed a lentiviral vector that can obtain physiological levels of expression of the WAS gene. It also demonstrated the efficacy and safety of the vector in mouse models of the disease.

Treatment involves taking samples of the patient’s hematopoietic stem cells carrying the genetic anomaly, then correcting them in the laboratory by introducing the healthy WAS gene using a lentiviral vector developed and produced by Genethon, then by Yposkesi. The corrected cells are then re-injected into the patient, who is first treated with chemotherapy. After re-injection, these stem cells will produce a variety of cell lines that make up the blood (white and red blood cells, platelets, etc.)

Genethon has conducted two international clinical trials including patients with severe forms of the disease in France (Necker-Enfants malades hospital, Paris) and in Great Britain, (Great Ormond Street Hospital, London). Another trial, for which Genethon has produced vectors, was also conducted in the United States (Children’s Hospital in Boston). This trial began in 2011 and enabled 10 patients to be treated, in Europe (the last patient completed the trial in the 3rd quarter of 2019). Following treatment, patients are monitored for 10 years: 2 years in the main trial, then 8 years in a safety follow-up trial.

Genethon obtained “Orphan drug” status from the European Medicines Agency (EMA) for this product, on 10/07/2013 under no. EU/3/13/1196.

Wiskott-Aldrich syndrome: what’s happening today?

The trials in France and the United Kingdom ended in 2017 and 2019 respectively. The results showed an overall improvement in the clinical condition of patients, involving reduction of severe eczema, of serious infections and bleeding, and improved platelet levels in the blood, varying according to patients.

Seven patients are still being monitored as part of the safety study, and the first patient was injected over nine years ago (2011).

Wiskott-Aldrich syndrome: find out more

The testimony of Anne Galy, Director of the U951 Research Unit (Inserm/Genethon) [in French]

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