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Gene Therapy

Gene Therapy

Gene therapy is a new treatment, currently only FDA approved for hemophilia B. There are several clinical trial studies taking place for other gene therapy treatments in both hemophilia A and B. 

Gene therapy is a treatment that provides your body with working copies of the gene to correct the disease or disorder. These genes provide the instructions to help your body produce the missing factor it needs to enable blood clotting. Gene therapy works differently in every person, so how much factor your body will produce and how long your body will be able to make its own factor is not known. It is important to work with your health care provider to determine if this treatment is best for you.

This section on gene therapy covers:

What is a gene?

Genes and Hemophilia B

What is gene therapy?

How does gene transfer therapy work?

Who is eligible for gene therapy?

Gene therapy precautions

What is a gene?

Our body contains instructions, called genes, that tell the body how to make proteins. Proteins are the building blocks for everything in the body. Some diseases or disorders, such as hemophilia or other bleeding disorders, happen when proteins are not made or do not work correctly. When a disease or disorder is caused by a gene passed down from one or both of your parents, it is called a genetic disease or genetic disorder. 

Genes and Hemophilia B

A person who has hemophilia B does not have the correct instructions (gene) to make factor IX (9). Factor IX (9) is part of a process called the clotting cascade that allows your blood to form a clot so that bleeding will stop. Without factor IX (9), the clotting cascade cannot work correctly. If your body does not produce enough factor IX (9), then bleeding without an injury (spontaneous bleeding) and bleeding that takes a long time to stop (prolonged bleeding) can happen. 

What is gene therapy?

Gene therapy is a way of treating a genetic disease or disorder by providing you with working copies of the gene to correct your disease or disorder. Gene therapy will allow your body to have the correct instructions to make the protein that is needed. There are many different approaches to gene therapy, including gene transfer, cell therapy, and gene editing, also known as CRISPR. The gene therapy treatment that is currently approved for hemophilia B uses gene transfer. Other types of gene therapy are being used in clinical trials. NHF has many resources that can help you understand gene therapy. Here is a 3 minute video that explains gene therapy:

If you want more information about gene therapy, please go to Future Therapies | Frequently Asked Questions | National Hemophilia Foundation

How does gene transfer therapy work?

To get a gene into the body, we need to have a way to protect the gene so that it doesn’t get broken down before it can start working. The method currently being used to protect the gene is to put the gene into a something called a vector. Common vectors used in gene therapy are viruses. The viruses used for gene therapy are changed so that they cannot make you sick. Instead, the virus protects the gene so that it can travel through the body. The virus that is used for gene therapy for hemophilia B is the adeno-associated virus (AAV). 

During gene therapy, the virus containing the correct instructions (genes) for making factor IX (9) are infused into the body. Infusion is done using a needle that goes into your vein and the process takes one to two hours. This is a one-time treatment and is done on site at a medical facility like a Hemophilia Treatment Center (HTC). You will have additional follow up visits for monitoring, but the infusion only happens once. This is very different than the other current therapies for hemophilia B which require treatment weekly or even multiple times a week.

After receiving the gene therapy, your body will have the instructions for making factor IX (9). Gene therapy targets the liver cells which is where factor is produced. The instructions (genes) are released from the virus into the liver cells, where they tell the liver cells to produce factor IX (9). This factor IX (9) travels in the bloodstream and will allow your body to make a stable blood clot.

Who is eligible for gene therapy?

The gene therapy currently approved is called entracogene dezaparvovec-drib (brand name HEMGENIX®). It is for treatment in adults with hemophilia B who use factor IX (9) prophylaxis (prophy); are experiencing a current life-threatening bleeding episode; have a history of life-threatening bleeding episodes; or have repeated, spontaneous bleeding episodes. If you have an inhibitor to factor IX (9), meaning that your body attacks the factor IX (9) protein when it is given to you using factor replacement therapy, you are not currently eligible for treatment using gene therapy. There are other conditions that might prevent you from receiving gene therapy, including liver diseases like hepatitis. Other conditions that may not be related to your bleeding disorder, like heart disease, may also mean gene therapy isn’t a fit for you. It is important to work with your hematologist to determine if this treatment is best for you.

Gene therapy precautions

One-time only treatment
Once you have received gene therapy using an adeno-associated virus (AAV), you will not be able to have another treatment of gene therapy using this same virus. This is true even if your first gene therapy treatment does not work for you or stops working. The reason gene therapy can be used only one time is that your body will now recognize the virus and attack it if it sees this virus again. When your body attacks the virus, it will cause the virus to be unable to deliver the gene to the liver. If the gene cannot reach the liver cells, it will be unable to provide the instructions needed to make factor IX (9).

Potential damage to the liver
Once you take gene therapy, you will need to be closely monitored by your health care provider. You will have your blood checked every week for the first three months after your treatment. These weekly blood tests are done to check for any liver damage that may be caused by the gene therapy. They also check factor IX (9) levels to see how well the gene therapy is working. Treatment is given to patients with test results that show stress on the liver due to the gene therapy.

Potential for inflammation
Your body may react to the gene therapy causing an inflammatory response which is your body’s process of fighting against things that could cause harm like infections or injuries. Due to the high dose of viral particles needed to help your body produce factor you may require additional treatment with high dose steroids for a few weeks or months. Left untreated, this inflammatory response may be dangerous and may lead to a decrease in the production of factor IX (9). 

Potential for liver cancer
There is a small possibility that the DNA used for your gene therapy treatment will go to areas of the body where it does not belong. The result of this can be liver cancer in some cases. If you have an increased risk for liver cancer (including cirrhosis, hepatitis B or C, non-alcoholic fatty liver disease, or chronic alcohol consumption), you should receive annual ultrasound screenings and blood tests to monitor your liver the first five years after treatment.