Sickle cell disease (SCD) is a genetic disease of hemoglobin, a protein contained in red blood cells that transports oxygen through the body. In patients with SCD, a defect in the structure of hemoglobin results in a deformation of the red blood cells, which take a sickle shape.
The disease, which result in anemia (characterized by fatigability, dizziness, shortness of breath …), occlusion of blood vessels, stroke, sensitivity to infections and severe pain, is caused by poor blood circulation associated with the sickle-like shape of the red blood cells, which then block the small blood vessels.
It is the most widespread rare genetic disease in the world, affecting millions of people. The disease is widespread in Africa, where a newborn out of 65 suffers for SCD, but also in the capitals of Western Europe, where one person in 2000 is born with the disease. In the Caribbean, 0.4% of newborns have sickle-cell anemia. In France, the number of annual births of SCD-suffering children is estimated to be 300, making SCD the first genetic disease in the hexagon.
The main treatment used for this pathology is blood transfusion. This helps to restore an acceptable amount of normal red blood cells in the body and to eliminate or significantly reduce the symptoms of anemia and the risk of stroke. However, these repeated transfusions result in an accumulation of iron in the body of patients that, over time, can cause cardiac, hepatic and hormonal problems.
Today, Genethon develops a gene therapy based on correcting the genetic abnormality present in hematopoietic stem cells (HSCs) by inserting a functional copy of the defective gene into the genome. For this, HSCs from the patient’s bone marrow are removed, cultured and then transduced with a lentiviral vector carrying a “healthy” copy of the hemoglobin gene. The genetically corrected cells are then retransplanted into the patient.
The team of Dr. Fulvio Mavilio developed a lentiviral vector to transfer the therapeutic hemoglobin gene into the patient’s HSCs. It remains to validate the efficiency and safety of the vector. The batches of vector of clinical grade will be produced at YposKesi according to good manufacturing practices.