Inherited blood disorders: should you consider gene therapy?

Sickle cell disease and beta thalassemia are genetic disorders caused by mutations or variations to the HBB gene. This gene is the segment of DNA that contains instructions for making beta-globin, one of the main components of hemoglobin, which is one of the main components of red blood cells.

With debilitating symptoms, a risk of serious complications, and the challenges associated with long-term treatment (including cost), there is a great deal of interest in therapies that can potentially cure sickle cell disease and beta thalassemia.

For many years, the only potential cure for either condition was a stem cell transplant, also known as a bone marrow transplant.

Gene therapies have emerged as new potential cures for these conditions. If you or a loved one is considering gene therapy for sickle cell disease or beta thalassemia, below is a look at how it works and what you will need to discuss with your healthcare team.

What are sickle cell disease and beta thalassemia?

While we are discussing both, it’s important to remember that sickle cell disease and beta thalassemia are separate disorders caused by different genetic mutations.

Sickle cell disease

Sickle cell disease occurs when mutations to the HBB gene produce abnormal beta-globin, a subunit protein that is one of the main components of hemoglobin. This changes the shape of red blood cells, causing red blood cells to have a crescent or sickle shape. These sickle cells die off easily, leading to low numbers of red blood cells (anemia). Sickle cells can also become stuck in blood vessels, causing pain and organ damage.

Beta thalassemia

Beta thalassemia occurs when mutations to the HBB gene interfere with the body's ability to produce beta-globin. When there are low levels of beta-globin, there will be low levels of hemoglobin. In severe cases, this can lead to life-threatening anemia, as well as other serious complications—failure to thrive, bone deformities, and enlarged organs (such as enlarged spleen, liver, and heart). Severe symptoms typically begin in the first two years of a person’s life.

How does gene therapy treat sickle cell disease or beta thalassemia?

Gene therapies aim to alter or “fix” the mutations in the HBB gene that are the underlying causes of sickle cell disease and beta thalassemia. This is a long, multi-step process that involves collecting blood stem cells from the person being treated, modifying the genes inside those stem cells in a lab, and reintroducing the modified stem cells into the body.

While gene therapies have the potential to cure sickle cell disease and beta thalassemia, these therapies require a lot from the person being treated and their caregivers. Like stem cell transplants, gene therapy involves intensive chemotherapy to destroy existing bone marrow and make room for the modified blood stem cells. A person will need to stay at a hospital for a month or longer, and the recovery process can take up to a year. Gene therapy is also expensive.

Nevertheless, because of the impact that sickle cell disease and beta thalassemia can have on a person’s health and quality of life, these are therapies that many people will want to discuss with their healthcare teams.

What should you discuss with your healthcare team?

Choosing to pursue gene therapy as a treatment for sickle cell disease or beta thalassemia is a decision you will need to arrive at with your healthcare team, as well as your loved ones. In addition to understanding the process of gene therapy, it's also important to consider these factors and how they impact the possibility for this treatment:

• The age and overall health of the person considering treatment
• The severity of symptoms and the risk of complications
• How well the current treatment is working, and what other treatment options are available
• The risk of long-term side effects, including damage to organs, compromised immunity, and infertility, and how these risks compare to the potential benefits
• The recovery process, including the length of the hospital stay, time away from work or school, the care that a person will need during recovery, and how often they will need follow-up appointments after treatment
• The financial considerations, including insurance coverage, the out-of-pocket expenses, and the indirect costs (such as time away from work for the person being treated or family members)

Even with the potential risks and long-term recovery, gene therapy is a potentially life-changing treatment, and a significant breakthrough in how conditions like sickle cell disease and beta thalassemia can be treated.