First sickle-cell anemia patient in the world successfully treated with gene therapy

A 13 year-old patient with severe sickle-cell anemia received gene therapy in October 2014. The team led by Professor Marina Cavazzana administered the therapy in October 2014 in Necker-Enfants Malades and the Imagine Institute (AP-HP/INSERM/Université Paris Descartes) as part of a phase I/II clinical trial. The team worked with Professor Philippe Leboulch (French Alternative Energies and Atomic Energy Commission (CEA)/Faculty of Medicine in Paris-Sud and Harvard University), who developed the vector used in the treatment and directed the preclinical trials. The results of the novel treatment were full remission of clinical symptoms and correction of biological signs. Published in the New England Journal of Medicine on 2 March 2017 the results confirm the effectiveness of this therapeutic breakthrough. 

Sickle-cell anemia is a serious form of inherited chronic anemia. Patients have a mutation in the gene that codes for β-globine that causes the production of abnormal hemoglobin and sickle shaped (falciform) red blood cells. Problems faced by sufferers include attacks of sudden very severe pain caused by vaso-occlusive crises. Other consequences are lesions on all vital organs, much increased susceptibility to infection, iron overload in the blood and endocrine disorders. 7% of the world's population are estimated to be affected by hemoglobinopathies. Of these, sickle-cell anemia is considered to be the most common with 50 million people who are either carriers of the mutation – with the risk of passing on the disease – or sufferers. β-globin, sickle-cell anemia and β-thalassemia anomalies are the most common inherited diseases in the world, and occur more frequently than all other genetic diseases combined.

The clinical trial coordinated by Prof. Marina Cavazzana* took place at the AP-HP Necker-Enfants Malades hospital and Imagine Institute.

During phase I, hematopoietic stem cells (HSC) responsible for the production of all the cell lines were harvested from the patient's bone marrow. A gene therapy viral vector, or lentiviral vector, developed by Prof. Philippe Leboulch** to treat ß-thalassemia was then transduced into the cells to correct the mutation. The vector can carry complex long DNA segments and is being produced on a large scale by US firm bluebird bio.

The treated cells were then reinjected into the young patient intravenously in October 2014. In-patient treatment took place in the Pediatric Immunohematology Department of Necker-Enfants Malades hospital, working closely with Professor Stéphane Blanche and Dr. Jean-Antoine Ribeil.

Fifteen months after receiving the corrected cell graft, the patient is transfusion-independent, free of vaso-occlusive crises and has completely resumed normal physical activities and schooling. "We also note that the therapeutic protein expression from the vector, which is a powerful inhibitor of the pathological falciformation, is remarkably high and effective," said Prof. Philippe Leboulch.

"We want to develop new clinical trials with this gene therapy model and enroll a large cohort of patients with sickle-cell anemia from the Greater Paris area and France as a whole", added Prof. Marina Cavazzana


*Professor Marina Cavazzana - M.D., Ph.D. Professor of Hematology at Université Paris Descartes, Research Director at the Center for Clinical Research in Biotherapy, Necker-Enfants Malades hospital, AP-HP, ParisNecker Hospital, Paris, and joint Director of the Inserm Human Lymphohematopoietic research group at the Imagine Institute for Genetic Diseases, Paris, France.

**Professor Phillipe Leboulch, Professor of Medicine at Université Paris-Sud Faculty of Medicine, Senior Advisor in medical innovation to the CEA and International Scientific Director of the François Jacob Biology Institute, discovered the therapeutic vector used in the trial (paper published in Science in 2001) and directed the preclinical trials with colleague Dr. Emmanuel Payen (Inserm, CEA).


References: Gene Therapy in a Patient with Sickle Cell Disease 


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