By Yosef Scher, Senior Science and Technology Editor
This past week, the Food and Drug Administration (FDA) approved exa-cel, the first gene editing therapy prescribed for people in the United States. The gene editing technology uses CRISPR, the revolutionary technique pioneered by Nobel Laureate Jennifer Doudna, that allows scientists to make changes in the DNA directly using targeted molecular tools. According to some scientists, this gene-editing therapy has the potential to cure sickle cell disease. Still, others are skeptical about the hurdles that affected patients must overcome.
Sickle Cell Disease is a genetic disorder caused by mutations in the beta-globin gene. For someone to express the disease, the person must inherit two faulty genes from each parent. Although the condition affects more than 100,000 people in the United States and 20 million people worldwide, it predominantly affects African Americans. More specifically, in the United States alone, “1 in 500 African Americans” have the disease, and “approximately 300,000 infants are born with Sickle Cell Anemia annually.” While scientists have found ways to treat the disease, including prescribing medications and blood transfusions, until last week, no one had discovered a way to demonstrate that the disease could be a potential cure.
How exactly does exa-cel work? Scientists discovered a unique form of hemoglobin called Hemoglobin F found only in fetuses. Exa-cel directs an enzyme called Cas9 to the BCL11A gene that typically prevents the body from making Hemoglobin F after the fetus has developed. Cas9 then deactivates BCL11A in bone marrow stem cells, where red blood cells are made. Cas9 cuts out and replaces the defective DNA — with genes encoding defective sickle cells — with genes encoding red blood cells with a standard round shape. Although scientists have used bone marrow transplants in the past, in this new therapy, physicians remove a person’s bone marrow stem cells and edit them with exa-cel. This process destroys the rest of the person’s untreated bone marrow, and reinfuses the edited cells back into the patient’s body.
For the FDA to approve this treatment, the companies that manufacture the cure, Vertex and CRISPR Therapeutics, needed to submit extensive data showing the efficacy of their treatment. While the data indicated that exa-cel was effective at curing Sickle Cell Disease, the data only tracked patients for a year. As such, some doctors, such as Michael DeBaun, a hematologist at Vanderbilt University, are skeptical about advising patients to get the cure because of the possible side effects that could emerge in the coming years. Since there has not been enough time for doctors to see how this treatment may affect patients in the long term, many doctors feel that more research must be conducted before considering this treatment.
In addition to the lack of time allotted for testing the treatment, many people have other qualms about the treatment. For instance, even if the treatment is proven to be curative in the long term, doctors are still determining how patients will be able to afford the treatment, as estimates for the treatment have averaged around two million dollars. Moreover, insurance companies that would potentially pay for such treatment have already indicated that they will not do so without further testing for many years. Another problem that Dr. Debaum brought up that this treatment would take much longer than the standard blood marrow transplant that Sickle Cell patients receive nowadays. That being said, he does acknowledge that exa-cel is seemingly much more effective than the conventional blood marrow transplant option provided to patients.
Time will only tell if exa-cel will be the miracle cure for Sickle Cell Disease that Vertex and CRISPR Therapeutics pride their product on. In any case, the treatments these scientists and companies have provided the world with are significant breakthroughs for patients who have Sickle Cell Disease.