New gene therapy may be the next treatment for sickle cell disease

Sickle Cell Disease

Researchers at Dana-Farber/Children ‘s Hospital Cancer Center (DF / CHCC) are going to develop a gene therapy for sickle-cell disease. The new experiment, whose results were presented at the 54th Annual Meeting of the American Society of Hematology, was tested on laboratory animals and proved successful. The research team led by DF / CHCC ‘s Raffaele Renella, MD, PhD, Stuart H. Orkin, MD, and David A. Williams, MD, were able to activate a new form of hemoglobin that is not affected by sickle-cell disease.

Sickle cell disease, or sickle-cell anemia, is an inherited blood disorder characterized by a single mutation in a component of hemoglobin, the protein responsible for transporting oxygen in the blood. It should be noted that this disease is more common in people who live in tropical regions where malaria is prevalent. It also should be noted that those who wear a single sickle-cell gene, which is called sickle-cell trait, are resistant to malaria infection.

Sickle Cell disease

In sickle cell disease, red blood cells shows a rigid form (sickle shape) that can not carry oxygen properly and then all the body suffers. In this way patients with sickle cell disease develop symptoms due to oxygen deprivation on the one hand, and on the other hand, symptoms related to the abnormal form of hemoglobin because sickle-shaped red blood cells obstruct small blood vessels. These symptoms are known as vaso-occlusive crisis, sequestration crisis or haemolytic crisis. Chronic pain, ischemia, necrosis, stroke, chronic renal failure, pulmonary hypertension are just some of the manifestations of this disease.

Vaso-occlusive crises, sometimes the first manifestation of the disease, are characterized by pain of different intensity and duration and are associated with high morbidity. Crises begin and end abruptly and are  accompanied by fever, leukocytosis, and malaise. Other symptoms that occur are splenomegaly, anemia, cholelithiasis, retinitis, blindness, etc..

New gene therapy thought by scientists at DF / CHCC is based on a previous work which showed that the molecular switch called BCL11A could treat the disease. There are two main types of hemoglobin produced by the human body: fetal hemoglobin that is produced during prenatal period and shortly after birth, and adult hemoglobin. BCL11A is a transcription factor that determines the shift in hemoglobin production. What is interesting is that fetal hemoglobin reduces the symptoms and complications of sickle-cell disease. Using the combined lentiviral gene transfer / RNA interference approach, the researchers were able to increase fetal hemoglobin production in the mouse by 5 to 20 times. Even though there are studies done to correct sickle-cell disease, researchers have made important steps in this regard.