Gene therapy successfully treated sickle cell disease in a 15-year-old French boy, reported in a recent study carried out by the Reference Centre for Sickle Cell Disease, Necker Children's Hospital in Paris.

In October 2014, the boy was the first patient to be treated at Necker Children’s Hospital for sickle cell disease in a clinical trial with gene editing therapy. Doctors altered the code in his DNA by adding a specific “anti-sickling” gene to his stem cells.

Teen had severe internal damage

The low-oxygen state caused by sickle cell disease usually results in problems such as anaemia, lethargy, higher risk of stroke and infections and intense body pain. When the deformed cells block the flow of blood around the body, it can cause organ damage which can be fatal.

The teenage boy had suffered from vaso-occlusive crises, acute chest syndrome, and bilateral hip osteonecrosis, and had to have his spleen and gallbladder surgically removed.

The patient underwent hydroxyurea treatment, the only disease-modifying therapy for the inherited gene mutation disease, between ages two and nine years but was found to be ineffective. He had also received prophylactic red cell transfusions and iron chelation. To dilute his defective blood, every month, the teenager had to visit the hospital to undergo a blood transfusion.

Patient no longer requires routine transfusion

Doctors collected stem cells from his bone marrow, and treated them with a lentiviral vector carrying an anti-sickling gene. The cells were genetically altered to correct blood cell production and to compensate for the defect in his DNA. The treated stem cells were then re-injected the patient’s bloodstream.

At 12 months, the patient’s ratio of sickled cells to oxygen saturation levels was similar to those of his mother, a heterozygote. Thus far, the therapy has proved effective for 15 months and he is still doing well. According to the study, at the least, 50% of his blood cells are considered normal and healthy.

Philippe Leboulch, a professor at the University of Paris, explained, "So far the patient has no sign of the disease, no pain, no hospitalisation. He no longer requires a transfusion so we are quite pleased with that.”

"But of course we need to perform the same therapy in many patients to feel confident that it is robust enough to propose it as a mainstream therapy," he added.

“A huge step forward” in gene therapy application

Leboulch is hesitant about using the word “cure” as it is just the first patient to come through clinical trials, but it certainly gives hope for millions of people with the blood disorder. Sickle cell disease is known to affect mainly people of African, Caribbean, Middle Eastern, Eastern Mediterranean and Asian origin.

Gene therapy research has taken many years and progress has been in “small steps”, according to Deborah Gill from the Gene Medicine Research Group at University of Oxford.

“But here you have someone who has received gene therapy and has complete clinical remission - that's a huge step forward,” she added.

However, the expensive procedure that can only be carried out in cutting-edge hospitals and laboratories raised concern as most sickle cell patients are in Africa.

“This is one of the classic genetic diseases everyone learns about in freshman biology,” said Steven J Gray from the Gene Therapy Center at the University of North Carolina. “As someone who works in the area of gene therapy every day, the realistic prospect of curing sickle cell disease with gene therapy is simply astonishing.”

“This provides hope that the next generation of students will read about the devastation of this disease in history books only.” MIMS

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