Gene Therapy Researched As Potential Treatment For Sickle Cell Disease

Originally published May 16, 2019

Carriers of the disease sickle cell anemia may see a long term source of relief on the horizon. A new gene therapy, still in the clinical trial stage as of March 2019, involves the addition of a functional beta-globin gene to isolated stem cells that are then returned to the patient.

Sickle cell anemia also called sickle cell disease (SCD) is a heritable blood disorder that affects an individual’s hemoglobin, a protein in red blood cells that carries oxygen through the body. Rather than the round, pliant nature red blood cells take, in individuals with SCD the cells are stiff, sticky, and shaped like crescent moons. This slows and even blocks the proper flow of oxygen and can result in bouts of intense pain in the chest, joints, and even bones.

Sickle cell disease poses a benefit in combating malaria. Those with just one copy of the gene for faulty hemoglobin did not experience the symptoms of SCD and were not susceptible to developing malaria. The exact way in which SCD inhibits malaria is still subject to debate; many researchers believe the improper shape itself of the red blood cells prevents them from being infected, while a 2011 study suggests the SCD cells produce monoxide gas in a way that does not destroy malaria but does protect the host from it.

Despite this advantage against malaria, when the gene for improper hemoglobin characteristic of sickle cell disease is inherited from both parents, the results can be highly debilitating, even deadly. Swelling in the hands and feet, exhaustion, anemia, and jaundice can plague those with SCD. Pain can occur in bouts called crises or can develop into a constant ache. Eventually, SCD can cause organ damage.

Photo Credit: NIH

Developing an effective treatment for SCD can, ultimately, save lives. Currently, bone marrow transplants have become the primary approach to curing the disease. Patients with SCD are matched with a healthy donor, from whose bone marrow healthy stem cells are removed and injected into the recipient. The stem cells in question are cells that produce red blood cells, and once in the body of the afflicted individual, they resume producing healthy blood cells. Matches, however, are very difficult to come by, with only about 30% of SCD patients finding a match. Financial strain further reduces the opportunity to access this otherwise effective treatment. Even if a match is found and the procedure is paid for or covered by insurance, the immune system must be suppressed, a common necessity anytime donor cells must interact with a recipient host, to avoid any reactions.

In place of bone marrow transplants between two separate individuals, gene therapy using the patient’s own cells has become a newly explored treatment option. Clinical trials have so far successfully treated SCD in numerous patients. Rather than extracting healthy stem cells from a donor, gene therapy derives stem cells from the patient, completely eliminating the risks associated with host-recipient interactions. Stem cells are extracted and the relevant genes are edited; from there, the healthy cells are left alone to multiply, to allow for plentiful replacement back into the host.

Stem cells are cells in the body that have not yet taken on a final, specific form and function. By working with these particular biocomponents, researchers can direct their fate to produce more of the desired cell. It is for this reason they have become popular in gene therapy.

Gene therapy presents its own hurdles. Though treating and curing the disease can save money in the long run, the costs are still substantial. In addition, such treatment is not done in one visit; even after the healthy genes are put back into the patient’s bone marrow, follow-ups are required to ensure improvement is still being obtained, both for clinical procedural purposes and to confirm that the hemoglobin gene was inserted in the correct position of the genetic code.

100,000 people in America alone live with sickle cell disease. Gene therapy treatments so far remain in the trial period, and scientists are still encouraging candidates to get informed. Multiple clinical trials are being conducted across the United States and abroad. Mastering treatment for one condition using a certain approach can, and has, led to learning how to treat other conditions.

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