Sickle cell disease is a genetic disorder that causes red blood cells that transport oxygen throughout the body in the blood to develop a characteristic “sickle” shape. This condition results in anemia from increased red blood cell death and frequent pain crises from the sickled cells sticking together and forming clots. Historically, new treatments and therapies for sickle cell disease have lagged behind other genetic conditions, such as cystic fibrosis. However, a new study from the University of Chicago reports positive results from a new gene therapy treatment.
An ongoing clinical trial has been running testing out a new gene therapy using CRISPR-Cas9 technology in affected patients’ stem cells. Red blood cells contain four types of hemoglobin subunits, which bind together with iron to transport oxygen throughout the body. Fetal hemoglobin is typically only made as a fetus develops and stops after birth and has a different composition of hemoglobin chains (protein subunits) compared to adult hemoglobin. Fetal hemoglobin is composed of alpha and gamma chains while adult hemoglobin is composed of alpha and beta chains.
An example of red blood cell shapes seen in sickle cell disease. The distorted shape of the red blood cell, which should normally be circular, causes poor oxygen transport and clotting events, which are incredibly painful.
Image Source: Ed Reschke
Sickle cell disease specifically affects the beta chain distorting its shape causing the red blood cell to become sickled. Patients enrolled in this clinical trial had their hematopoietic stem cells, which give rise to the four major blood cell types including red blood cells, harvested. CRISPR-Cas9 technology was used to edit the genes in this cell to specifically enhance the cell’s production of the gamma chain to increase the formation of fetal hemoglobin. This therapy would allow the gamma chain to replace the improper beta chains and increase the number of healthy red blood cells.
Results from this trial so far are promising with patients who received the CRISPR-Cas9 edited stem cells reporting fewer disease symptoms. Specifically, patients are reporting a decrease in vaso-occlusive, or blood clotting, events that result in a significant pain crisis and the need to be admitted to the hospital.
This clinical trial represents a step forward in the use of gene-editing technology as a therapy for genetic conditions. In the United States alone, over 100,000 individuals are affected by sickle cell disease, so a promising therapy that can reduce some of the severe symptoms of the condition can greatly improve quality of life and the ability for people to live more independent lives.
Featured Image Source: ckybe
