Research Breakthrough

Gene therapy trial results in complete remission of sickle cell disease

A gene therapy trial in a 13-year-old patient with sickle cell disease has enabled complete remission of clinical signs of disease and correction of biological indicators.

Results of the trial begun in October 2014 are published in the 2 March 2017 issue of New England Jounal of Medicine.

Prof. Marina Cavazzana lead the team that conducted the research at Necker Children’s Hospital, AP-HP and the Imagine Institute (AP-HP / Inserm / Université Paris Descartes. The study was conducted in collaboration with Prof. Philippe Leboulch (CEA / University Faculties of Medicine of Paris-Sud and Harvard University) who developed the vector used and directed preclinical studies.

Sickle cell disease is characterized by the production of an abnormal haemoglobin and deformed (sickle-shaped) erythrocytes, due to a mutation in the gene encoding the b-globin. This disease causes episodes of very severe pain caused by vaso-occlusive crises. It also causes lesions of all vital organs, sensitivity to infections, as well as iron overload and endocrine disorders. It is estimated that hemoglobinopathies affect 7% of the world population. Among them, sickle cell disease is considered the most common with 50 million people carrying the mutation.

The first phase of the trial consisted of collecting hematopoietic stem cells, enabling the production of all the lineages of blood cells, in the bone marrow of the patient. A vector1 virus carrying a therapeutic gene, already developed to treat beta- thalassemia, was then introduced into these cells.

This lentiviral vector capable of carrying long complex DNA segments, was developed by Prof Leboulch.

The treated cells were then reinjected intravenously into the young patient in October 2014. The teenager was then supported during his hospitalization in the paediatric immunohaematology service of the Necker Children’s Hospital.

Fifteen months after transplantation of genetically corrected cells, the patient no longer needs to be transfused, no longer suffers from vaso-occlusive crises, and has fully resumed his physical and school activities, the researchers noted.

“We also note that the expression of the therapeutic protein from the vector, which inhibits pathological sickle cell formation, is remarkably strong and effective,” said Prof Leboulch.

Prof Cavazzana said: “We hope, with this gene therapy approach, to develop future clinical trials and include a significant number of patients with sickle cell disease.”

  • doi: 10.1056/NEJMoa1609677

Sickle cell disease in Arab states

Sickle cell disease is highly prevalent in the Arab states. Some of the world¡¦s highest frequencies of the disease are seen in Saudi Arabia (5.2%), Oman (3.8%), UAE (1.9%). Lower values are observed in Yemen (0.95%), Bahrain (0.7%), and other Arab countries. Studies in population genetics revealed that the extent of clinical severity in sickle cell disease is related to the genetic back- ground (haplotype) of the affected individual. In the Arabian Peninsula, sickle cell disease occurs in association with two backgrounds: the African haplotype, a severe type, mostly occurring in patients residing in the western regions of the Arabian Peninsula, and the Arabian/Asian haplotype, a moderate type, mostly occurring in patients residing in the eastern regions of the Arabian Peninsula. The high prevalence of the disease has prompted extensive studies on it, and almost all Arab countries have undertaken vast amounts of work on the clinical features, genetics, and management of sickle cell disease. Several Arab states have taken extensive measures to reduce the rates of sickle cell disease. Screening programs are one of the most effective of such strategies. Especially in the countries of the Gulf Cooperation Council (GCC), screening of students, infants, and mandatory screening of couples before their marriage have been very effective.

  • Centre for Arab Genomic Studies




Date of upload: 14th May 2017

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