Scientific and medical advances in sickle cell disease

On World Sickle Cell Day, find out how research teams and physicians at the Imagine Institute are fighting this most common genetic disease affecting the blood. Clinical trials of gene therapy, in particular, are showing very positive long-term effects in patients who have not been able to receive a bone marrow transplant. In parallel, researchers are developing innovative gene therapy approaches that are potentially more effective and less costly.

Published on 15.06.2022

Research Acceleration

With 350,000 new cases diagnosed each year, sickle cell disease is the most common genetic disease. It affects 50 million people in the world. Its cause? A mutation in the gene coding for hemoglobin, a protein that makes up the red blood cells and whose role is to transport oxygen in the blood to the organs. This mutation (a simple change of letter in the genetic code) causes a defect in the structure of hemoglobin. This causes the red blood cells to become rigid and sickle-shaped, clogging the blood vessels. This leads to extremely painful attacks in patients, severe anemia and an increased risk of infections, with a progressive loss of organ function.

The only curative treatment is a blood stem cell transplant, taken from the bone marrow of compatible donors. However, this approach is limited by the lack of availability of these donors: they are found in only 25% of cases. There are therefore treatments available to reduce the pain of sickle cell patients, including blood transfusion, which consists of punctually replacing the stock of diseased red blood cells with healthy red blood cells, iron chelators to reduce its overload, and painkillers.

The problem is that these regular treatments are cumbersome and target the consequences rather than the causes of the disease, which, moreover, progresses with severe organ damage. An alternative is gene therapy, which we are developing at the Institut Imagine, both through clinical trials conducted at the Necker-Enfants Malades Hospital (AP-HP) and through fundamental research aimed at developing the gene therapies of the future. It consists of using a transporter capable of carrying a new genetic sequence to the nucleus of the cell. This new sequence is then integrated into the genome, before being translated and transcribed into healthy hemoglobin. In 2022, the team of Prof. Marina Cavazzana, a pediatrician, director of the biotherapy department at the Necker-Enfants Malades Hospital and director of the Clinical Investigation Center for Biotherapy, affiliated with the Institut Imagine (Inserm, AP-HP, University of Paris) published in Nature Medicine, very encouraging results of the long-term follow-up of sickle cell patients treated by gene therapy.

"Patients treated with gene therapy no longer need blood transfusions and have stopped all pain medications, so there is a clinical and biological cure. This proves that gene therapy can represent an alternative solution in the case where these patients lack an HLA-matched donor."  

Pr Marina Cavazzana

At the same time, fundamental research is in full swing in the laboratories. Annarita Miccio's team, director of the "Chromatin and gene regulation during development" laboratory, is developing the gene therapies of tomorrow, with new viral vectors using innovative processes, in particular CRISPR-Cas-9 molecular scissors, capable of cutting DNA anywhere in the genome. Discover his team in pictures in the video of our Into The Lab series, dedicated to the research teams of the Institut Imagine.

"My dream as a researcher [...] is to not only cure patients, but more importantly a large number of patients, by reducing the cost of these gene therapies"  

Annarita Miccio, Laboratory Director