Basics of gene therapy.

Sickle cell disease (SCD) is a group of blood disorders that happen because a mutated (changed) gene makes a different type of hemoglobin. Healthy red blood cells have hemoglobin A and are round and soft. They move easily through small blood vessels to carry oxygen to all parts of the body. With SCD, you make a different type of hemoglobin called hemoglobin S. Hemoglobin S is c-shaped like the farm tool called a sickle. When these sickled cells move through small blood vessels, they get stuck and can block the flow of blood and oxygen. This can damage organs and cause health problems.

About gene therapy.

Several medications are available to treat SCD and more are on the way. Each drug works in its own way to help prevent problems. But, none of them target the actual cause of SCD. That’s where gene therapy can help. Scientists are studying if and how gene therapy might work for SCD.

SCD is caused by a mutation (change) in the gene that makes hemoglobin. Genes are bits of information found in the cells of your body. They make up the “recipe” for a person. Sometimes genes mutate, which causes them to not work well. In SCD, a mutated gene causes the red blood cells to make hemoglobin S instead of hemoglobin A. Gene therapy could help cure SCD by changing this gene back to a healthy one.

How gene therapy may work.

Gene therapy may cure SCD by two main ways:

• Replacing the mutated gene with a healthy one. Gene therapy for SCD targets stem cells. Stem cells are the most basic cells in the bone marrow. Some stem cells will turn into red blood cells, the cells that carry hemoglobin. Scientists are learning how to take the stem cells out of a person with SCD, then remove the mutated gene and replace it with a normal one. When the stem cells are sent back to the bone marrow, they should start making new red blood cells with hemoglobin A.
• Helping your body make more healthy hemoglobin. When you are born, the main type of hemoglobin you have is fetal hemoglobin. Fetal hemoglobin doesn’t sickle. When you are about six months old, a different gene tells the bone marrow to stop making fetal hemoglobin and start making adult hemoglobin. That’s fine if your body makes hemoglobin A. But it isn’t helpful if you have SCD and your adult hemoglobin is hemoglobin S. Gene therapy helps by blocking the gene that “turns off” fetal hemoglobin. That way, your body can keep making more healthy hemoglobin that won’t sickle.

What you can expect.

First your stem cells will be collected from a vein in the arm using a special machine. Your own stem cells play a major part in gene therapy. The scientists make copies of the gene that properly make hemoglobin A. These copies of the gene are added to your stem cells that were collected to make the gene therapy.

The next step is to get your bone marrow ready for gene therapy. You’ll go through “conditioning.” This is a process that clears out the faulty bone marrow cells to make room for the new normal cells. You’ll receive a medication that destroys the mutated cells in your bone marrow. It’s an intense, but needed, step in gene therapy. And finally, you’ll receive the gene therapy intravenously (an infusion given into the vein). This is a one-time infusion. Afterwards, you’ll need close monitoring while your cells take the time needed to produce these new cells. This entire process will take several weeks.

After gene therapy, you’ll have close follow up for many years. Your health care team will check for safety and track how well the gene therapy is working. They’ll also collect information that may help other people with SCD who are thinking about gene therapy.

There is still a lot of research to be done for gene therapy. But it may be a promising treatment option for SCD. Talk to your doctor or CVS Specialty® CareTeam to learn more about gene therapy.

This information is not a substitute for medical advice or treatment. Talk to your doctor or CVS Specialty® CareTeam to learn more about gene therapy.