Sickle cell anemia, a type of sickle cell disease (SCD), is a genetic condition that affects your red blood cells (RBCs). It affects around
Healthy RBCs are donut-shaped. They’re flexible and can easily move through the tiniest of your blood vessels. However, if you have sickle cell anemia or other types of SCD, affected hemoglobin in your blood causes your RBCs to be rigid and shaped like the letter “C” or a sickle.
Sickle-shaped RBCs are prone to getting stuck in small vessels, making it hard for blood to reach many parts of your body. This can cause pain, infections, and tissue damage.
Because of these factors, current treatment options are often not possible or recommended for people with SCD.
However, a new cure for SCD has recently appeared on the horizon: gene therapy. What is it, and when can you receive this treatment? Read on to find out.
What is gene therapy?
Each of your cells contains DNA, a molecular code that makes up genes. Think of it as a set of instructions on how to build and support each cell inside your body.
These instructions can sometimes have typos, or mutations. Most of the time, mutations aren’t of major consequence, but sometimes they can hit critical parts of your genes. This can harm your cells’ ability to properly perform their assigned task. This is what happens in SCD.
Gene therapy uses specialized molecular tools called CRISPR-Cas9 to fix faulty genes and restore the normal function of your cells.
There are a couple of ways
In this approach, scientists use CRISPR-Cas9 to cut your DNA at the sites of the mutations and replace them with the “correct” code. This is called gene editing based on its similarity to the work of a book editor.
When used in SCD, CRISPR-Cas9 edits mutations in your hemoglobin genes. This restores hemoglobin’s ability to capture oxygen and gives RBCs back their healthy shape.
Switching on unused genes
In another approach, CRISPR-Cas9 is used to switch on a gene that encodes a different kind of hemoglobin called fetal hemoglobin. This hemoglobin normally only works during fetal development.
Shortly after a baby is born, their RBCs stop making fetal hemoglobin, replacing it with “adult” hemoglobin. If your adult hemoglobin contains SCD mutations, switching on your fetal hemoglobin can help skew the balance in favor of healthy RBCs.
There are other possibilities for CRISPR-Cas9 sickle cell therapies, but they haven’t yet received approval for clinical trials.
The first step of gene therapy is making a carrier that will place all the necessary tools inside your cells.
Scientists use a carrier, or a vector, to deliver CRISPR-Cas9 to its destination. Some of the vectors are based on viruses. These are inactivated viruses, so they can’t cause disease during the procedure.
In the next step, doctors will collect your bone marrow cells (cells that make blood) and work in the lab to inject them with the vector. At this step, CRISPR-Cas9 begins its work to edit your hemoglobin gene. This step can take a few months.
In the final step, doctors reintroduce modified bone marrow cells into your body via an intravenous (IV) infusion. Before this procedure, you most likely will receive chemotherapy treatment to eliminate the remaining abnormal cells from your bone marrow.
Although gene therapy for SCD isn’t currently available to most people, this may change in a few years. Clinical trials are ongoing, and some successful results are already available.
One of the first trials used a therapy called CTX001, which works to switch on fetal hemoglobin. As of 2021, more than a year after the infusion of modified bone marrow cells, trial participants remain free of their disease.
Other trials that either aim to edit abnormal adult hemoglobin or switch on fetal hemoglobin are ongoing and expect results in the near future.
Although the research is still ongoing, the first results show high efficacy of gene therapy for SCD treatment. Researchers still need to complete long-term observations to ensure that people remain disease-free and without any new health concerns.
Gene therapy is much safer than the only currently available cure, bone marrow transplant. While bone marrow transplant requires cells from a closely matched donor, gene therapy cures your own cells. This decreases many health risks and eliminates the need for immunosuppressive drugs, which you otherwise would need to take for the rest of your life.
Clinical trials are currently trying to establish what risks, if any, are associated with gene therapy in SCD. We won’t fully understand the risks until researchers complete trials and publish results.
However, many people are concerned with the chemotherapy step of the treatment. Chemotherapy can weaken your immune system, cause hair loss, and result in infertility.
In addition, gene therapy might increase your risk of getting cancer. Although researchers haven’t yet observed this in clinical trials for SCD, they need more time to determine whether gene therapy can cause cancer or other health issues.
How much does gene therapy for sickle cell anemia cost?
Is gene therapy for sickle cell anemia approved by the FDA?
As of June 2022, the Food and Drug Administration (FDA) hasn’t yet approved gene therapy for SCD. However, with several drugs in late-stage clinical trials, we can expect first approvals in the near future.
Can gene therapy cure beta thalassemia?
Beta thalassemia is another genetic disorder that affects your hemoglobin and RBCs. Although no cure aside from a bone marrow transplant is currently available, the first results of late-stage clinical trials suggest that gene therapy can potentially cure beta thalassemia.
Gene therapy may treat SCD by editing DNA in hemoglobin genes to stop the disease. It can be done by either fixing the faulty hemoglobin gene or turning on a different, healthy hemoglobin gene.
Although gene therapy for SCD isn’t currently available for most people, this may change soon. Several late-stage trials are in process, and some show early successful results.
Although you can expect gene therapy to be very costly, it still might cost less than what people with SCD currently pay for lifelong disease management.