Sickle cell anemia is a disorder that affects the hemoglobin molecule, which is present in red blood cell delivering oxygen to cells throughout the body. The shape of the red blood cell changes to crescent or sickle shape. This blocks the red blood cell from passing through the blood vessels and delivering oxygen to organs and tissues. The symptoms are anemia, organ damage, and repeated pain episodes.
Researchers performed several preclinical research where a new gene therapy treatment for sickle cell anemia is altering the disease symptoms in two patients and showing early potential for transportability to resource-challenged parts of the world where sickle-cell anemia is very common. The treatment of the first patient and a six months treatment of the second patient have shown remarkable improvement in the quality of life, resulting in the elimination of chronic pain and sickling events. If this treatment is sustained, it will provide a transportable, safe, and feasible gene therapy for SCA patients.
In Cincinnati Children's, the gene therapy took a modified gamma globin lentivirus vector to transfer a healthy fetal hemoglobin gene called hematopoietic stem cells into a patient blood stem cells. The modification of lentivirus resists it from causing illness. Some adults constantly produce fetal hemoglobin (HbF), which prevents the red blood cell from sickling. Generally, fetal hemoglobin stops after birth. The new gene therapy was able to place a fetal hemoglobin gene in the bone marrow cells that cannot stop.
In a clean lab, the cells were collected from the SCA patient and genetically reprogrammed with a modified lentivirus vector. The patient’s bone marrow was then preconditioned with one low-dose chemotherapy, and finally, gene-corrected cells were infused back into the patient. The patients recovered within a week to 10 days and also from the chemotherapy effects by two weeks. This method is less toxic and expensive than myeloablative preconditioning which is used in bone marrow transplants. Myeloablative conditioning uses high-intensity chemotherapy for preparing a transplant of the patient’s bone marrow for healthy gene-corrected blood stem cells (HSCs). This results in low blood counts and other side effects.
The main goal was to treat SCA by reduced-intensity chemotherapy in hospitals. The study will also tell investigators of the long-term clinical benefit of this therapy to patients with severe SCA.