Sickle cell anemia, a type of sickle cell disease (SCD), is a genetic condition that affects your red blood cells (RBCs). It affects around 100,000 Americans and is most common in people of African, Hispanic, and South Asian descent.

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.

It is hard for blood to reach many parts of your body because of the small vessels that are prone to getting stuck in. This can cause pain and infections.

Until recently, bone marrow transplants were the only cure for SCD. Finding a matching donor can be a major obstacle. There are also significant risks associated with this treatment.

Current treatment options are not usually recommended for people with the disease.

Gene therapy is a new cure for SCD. What is this treatment and when can you receive it? 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 have errors. Sometimes, the effects of the mutations are minor, but sometimes they can hit critical parts of your genes. This can hurt your cells ability to perform their assigned task. This is what happens in the police department.

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 gene therapy can tackle SCD. Both of these mechanisms target your hemoglobin genes. Hemoglobin helps your RBCs deliver oxygen from your lungs to the rest of your body.

Gene editing

Scientists use the tool of the CRISPR-Cas9 to cut your genes at the sites of your previous errors and replace them with the correct code. Gene editing is similar to the work of a book editor.

In the case of SCD, the edits to your hemoglobin genes are made using the CRISPR-Cas9 technology. This restores the ability of hemoglobin to capture oxygen and give the RBCs 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.

After a baby is born, the fetal hemoglobin in the RBCs is replaced by adult hemoglobin. If your adult hemoglobin contains a certain type of genetic abnormality, you can switch on your fetal hemoglobin to help skew the balance.

“There are other options for treating sickle cell disease, but they haven’t received approval for clinical trials.”

The first step in gene therapy is to make a carrier that will hold all the tools.

“Scientists use a carrier to deliver a drug. Some of the images 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.

Illustrated by Jason Hoffman

Although gene therapy for SCD is not currently available to most people, it may change in a few years. Some successful results from clinical trials are 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.

The trials that aim to change adult and fetal hemoglobin are still going on and should have results in the near future.

The first results show high efficacy of gene therapy for the treatment of the disease. Researchers still need to complete long-term observations to ensure that people remain disease-free.

Benefits

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.

Risks

“Clinical trials are trying to figure out what risks are associated with gene therapy. We don’t fully understand the risks until trials are complete and results are published.”

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.

Gene therapy might increase your risk of cancer. Researchers need more time to determine if gene therapy can cause cancer or other health issues.

How much does gene therapy for sickle cell anemia cost?

A recent study estimated that people with SCD may expect to pay up to $1.85 million for the whole treatment cycle. However, gene therapy still might be less expensive than treating chronic problems from the disease over several decades. It’s unknown whether health insurance providers will offer coverage for this type of treatment.

Is gene therapy for sickle cell anemia approved by the FDA?

“The FDA hasn’t approved gene therapy for the disease as of June 2022. We can expect first approvals in the near future with several drugs in late-stage clinical trials.”

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 be able to stop the disease by editing genes. It can be done by either fixing the faulty hemoglobin gene or turning on a different healthy hemoglobin gene.

Although gene therapy for SCD is not currently available for most people, it may change soon. Some late-stage trials show early success.

Gene therapy is expensive, but it might be less expensive than disease management for people with the disease.