What Is Gene Therapy for Sickle Cell Disease?

Gene therapy is an exciting therapy now being studied for the treatment of sickle cell disease. The treatment is only currently available as a part of clinical trials. Researchers are currently optimistic that gene therapy treatment will be successfully shown to cure the disease.

Overview of Sickle Cell Disease

Sickle cell disease is a heritable medical condition resulting from a genetic mutation. The mutation causes a change in the way a specific protein is made, hemoglobin. Hemoglobin is what makes up red blood cells, the cells that transport oxygen around your body.

Because of the mutation, red blood cells in people with this disease take on an abnormal, “sickled” shape. The cells are fragile and prone to breakdown. This can cause anemia (reduced number of functioning red blood cells), resulting in symptoms like fatigue and pale skin.

These abnormally shaped red blood cells also tend to form blood clots that block blood vessels. This can cause problems like:

• Episodes of extreme pain
• Kidney failure
• Stunted growth
• Elevated blood pressure
• Lung problems
• Strokes

These complications can be severe and life-threatening. Not surprisingly, the disease also takes an enormous emotional toll. It is more common in people with ancestry from Africa, South Asia, the Middle East, and the Mediterranean. Worldwide, more than 300,000 infants are born with the disease every year.

What Are Clinical Trials?

Clinical trials are a stage of medical research used to prove that a treatment is safe and effective in people with the condition. Researchers want to make very sure that a treatment has reasonable safety risks and is effective before it can become available to the general public.

That means that the full risks and benefits of the treatment have not been assessed in a large number of people.

People who become part of a clinical trial are usually randomized to either receive the therapy being studied, or to become part of a "control" group that does not receive this treatment. Often, randomized clinical trials are "blinded," so that neither the patient nor their healthcare providers know which study group they are in. Any side effects are also carefully noted, and if a study appears unsafe, it is stopped early. But not everyone qualifies to be included in such trials, and you might need to receive treatment at a highly specialized medical center to be included.

Currently, gene therapy treatments are undergoing clinical trials in the United States, and some may be still looking for people to join. Don’t hesitate to discuss it with your healthcare provider if this interests you. There are risks but also potential benefits to being included in a clinical trial before a treatment has been studied in a large number of people.

For the most up-to-date information on clinical trials for people with sickle cell disease, check out the National Institutes of Health clinical trials database and search for “gene therapy” and “sickle cell disease.”

Current Treatments

Bone Marrow Transplant

Currently, the only treatment that can cure sickle cell disease is a bone marrow transplant. The person with sickle cell disease is exposed to chemotherapy. This destroys the stem cells present in the bone marrow, the cells that later go on to become red blood cells (and other types of blood cells). Then, they are transplanted with stem cells that someone else has given through a bone marrow donation.

There are some serious risks with this procedure, such as infection. However, if the donor is a sibling with an appropriate bone marrow match (also called an HLA match), transplants successfully cure the disease about 85% of the time. But in only about 25% of cases will a sibling be an HLA match.

Rarely, a matched donor might be available from someone who is not a relative. Less than 20% of sickle cell patients have an appropriate donor available for bone marrow transplant.

Hydroxyurea

The most commonly used treatment for sickle cell disease is hydroxyurea. It helps the body keep producing another form of hemoglobin that isn’t affected by sickle cell disease (called fetal hemoglobin). Other than a bone marrow transplant, hydroxyurea has been the only treatment available that affects the disease itself. A new drug, voxelotor, approved by the FDA in November 2019, makes sickle cells less likely to bind to each other (called polymerization).

Other treatments available can help lessen disease complications, but don't affect the disease itself.

People taking hydroxyurea need to have their blood counts regularly monitored. Hydroxyurea also doesn’t seem to work well for some patients. 

How Sickle Cell Gene Therapy Works

The idea behind sickle cell gene therapy is that a person would receive some sort of gene that would allow their red blood cells to function normally. Theoretically, this would allow the disease to be cured. This takes several steps.

Stem Cell Removal

First, the affected person would have some of their own stem cells removed. Depending on the exact procedure, this might involve taking stem cells from the bone marrow or from the circulating blood. Stem cells are cells that later mature to become red blood cells. Unlike a bone marrow transplant, with this gene therapy, an affected person receives their own treated stem cells.

Insertion of New Gene

Scientists would then insert genetic material into these stem cells in a laboratory. Researchers have studied a couple of different genes to target. For example, in one model, the researcher would insert a “good version” of the affected hemoglobin gene. In another model, researchers insert a gene that keeps fetal hemoglobin produced.

In both cases, part of a virus called a vector is used to help insert the new gene into the stem cells. Hearing that researchers use part of a virus can be scary for some people. But the vector is carefully prepared so there is no possibility of causing any type of illness. Scientists just use these parts of viruses because they can already efficiently insert the new gene inside a person’s DNA.

In either case, the new stem cells should be able to produce red blood cells that function normally.

Chemotherapy

Meanwhile, the person with sickle cell receives a few days of chemotherapy. This can be intense, as it knocks down the individual’s immune system and can cause other side effects. The idea is to kill as many of the remaining affected stem cells as possible.

Infusion of Patient's Own Stem Cells With New Gene

Next, the patient would receive an infusion of their own stem cells, the ones that have now had the new genetic insertion. The idea is that most of the patient's stem cells would now be ones that make red blood cells that don’t sickle. Ideally, this would cure the symptoms of the disease. 

Advantages of Gene Therapy

The main advantage of gene therapy is that it is a potentially curative treatment, like bone marrow transplant. After the therapy, one would no longer be at risk of health crises from sickle cell disease.

Also, some people who receive stem cell transplants have to take immunosuppressive drugs for the rest of their lives, which can have some significant side effects. People receiving their own treated stem cells shouldn’t need to do this.

Risks

One of the main purposes of these trials is to get a fuller idea of the risks or side effects that might come with treatment.

If ongoing clinical trials show that the risks are too significant, the treatment will not be approved for general use. However, even if current clinical trials are not successful, another specific type of gene therapy for sickle cell disease might eventually be approved.

However, in general, there is a risk that gene therapy can increase the risk of getting cancer. In the past, other gene therapies for different medical conditions have shown such a risk, as well as a risk for a number of other toxic side effects. These have not been observed in the particular gene therapy treatments for sickle cell currently being studied. Because the technique is a relatively new one, some of the risks might not be easily predicted.

Also, many people are concerned about the chemotherapy necessary for gene therapy for sickle cell disease. This might cause a number of different side effects like lowered immunity (leading to infection), hair loss, and infertility. However, chemotherapy is also a component of bone-marrow transplant.

The gene therapy approach seemed to be a good one when researchers tried it in mouse models of sickle cell. A few people have also had such treatment successfully.

Potential Costs

One of the potential downsides for this treatment is the expense. It’s estimated that the full treatment might cost between $500,000 to $700,000 spread out over several years. However, this might in total be less expensive than treating the chronic problems from the disease over several decades, not to mention the personal benefits.

Insurers in the United States may be hesitant about providing medical approval for this treatment. It’s not clear how much patients personally would be expected to pay.

A Word From Verywell

Gene therapy for sickle cell disease is still in its early stages, but there is hope that it will eventually be successful. If you are excited about this idea, don’t hesitate to contact your healthcare provider to see if you might be able to be included in early trials. Or you can just begin to think about the possibility and see how research progresses. It's best not to neglect your health in the meantime—it’s very important that people with sickle cell disease receive their daily treatment as well as frequent health checks.

It’s also important to seek treatment as soon as possible for any complications. Early intervention is key in coping and managing your condition.