Blood Disorders

Sickle cell disease, beta thalassemia, and Fanconi anemia are a collection of inherited blood disorders caused by faulty genes that keep the elements of our blood from doing their unique jobs. Because of their genetic roots, gene therapy might offer a potential way to fight symptoms.

About Blood Disorders

Blood is very important to our body. There are different components that make up our blood, each serving different functions. Red blood cells supply oxygen to cells and tissues, while also helping to remove waste. White blood cells fight infectious intruders like bacteria. Platelets control blood clotting, which is vital to helping your body control a cut or an injury.

When our blood cells and platelets can’t operate efficiently, there are severe consequences for our body. Reduced blood flow and reduced oxygen in our bodies can cause weakness, fatigue, slowed growth, severe pain and other serious complications that make it difficult to go about daily life.

Usually, a blood disorder is detected in a patient by doing a blood test, such as a complete blood count (CBC). Since blood disorders are inherited, people who are considering having a child are encouraged to meet with a genetic counselor to assess risks.

Goal of Gene Therapy

The aim for blood disorder gene therapy is a one-time administration that targets the cause of the disease. By targeting the exact cause of the disease—a faulty gene—gene therapy eliminates the need for recurring interventions and there is no need for a donor. Unlike a bone marrow transplant, a patient’s own cells are used. Here’s an example of how this works:

Fanconi anemia is a disorder that stops the bone marrow from making enough red blood cells, white blood cells and platelets. This is because of a mutation in one of several genes. However, an ex-vivo gene therapy approach can target these faulty genes to help a patient’s body function properly. By the way, “ex-vivo” means that the treatment occurs outside of the body— as opposed to an “in-vivo” treatment which happens inside the body. In this approach, a patient’s hematopoietic stem cells, also known as HSCs, are removed from the body. These stem cells are cells that can serve a variety of roles. Our HSCs give rise to red and white blood cells and platelet cells.

A vector, which is often a virus, is able to deliver the new working gene into the HSCs. Don’t worry, the viral genes that are known to cause disease have been removed. The HSCs are then returned to the body, helping correct the disease. It is important to note that gene therapy is not a cure for the disease, but instead a means to control disease progression.

Participate in Clinical Trials

You may be curious how patients can participate in clinical trials as a way to receive an investigational treatment at no cost, while also benefiting the medical community and others who have the disease. If you think you or your child may be eligible for a clinical trial, it’s best to speak with your primary care physician or hematologist first to learn more and determine if it is right for you. Then, the individual must meet the eligibility criteria, which can be based on the age at the time of dosing, physical ability, past medical treatment and more.

Get Involved

At this time, we do not know if or when these gene therapy treatments will be approved by the FDA and available commercially. The overall process to ensure that the treatment is safe and effective can take several years. One way you can help is to become involved with a patient advocacy organization. They work hard to fund research, raise awareness and advocate for treatment development. They’re also a great way to connect with other families and patients affected by blood disorders, if you’re looking for support and advice. The diseases may be rare, but you're not alone.

A number of organizations provide patients and families with resources in managing inherited blood disorders:

Treatment Pipeline

Beta Thalassemia: ST-400

Sanofi Genzyme and Sangamo are working together on collaborative gene-edited cell therapy projects, including ST-400, a treatment designed to increase fetal hemoglobin in patients with Beta Thalassemia. The ST-400 gene therapy is currently in Phase I/II trials, which combine aspects of Phase I and II trials into single studies in order to accelerate drug development.

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Sickle Cell Disease: BIVV003

Sanofi Genzyme and Sangamo are also using ZFN gene-editing technology for the treatment of sickle cell disease as part of Phase I/II trials. Zinc finger nuclease gene-editing is performed ex-vivo and targets the BCL11A gene to increase production of fetal hemoglobin.

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Sickle Cell Disease: RVT-1801

Aruvant Sciences has an ongoing clinical study of a lentiviral gene therapy to increase functioning red blood cells. This approach is also being investigated for beta thalassemia.

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Transfusion-Dependent Beta Thalassemia: LentiGlobin

Bluebird Bio, a biotechnology company, is developing a gene therapy called LentiGlobin for the treatment of transfusion-dependent Beta Thalassemia. “Transfusion-dependent” means the disease is so severe that the patients require a lifetime of chronic blood transfusions to survive.

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Sickle Cell Disease: LentiGlobin

LentiGlobin is also designed to help patients with severe sickle cell disease. Patients with the disease have a lifelong need for comprehensive care, including chronic transfusions. A gene therapy treatment has the potential to prevent or reduce damaging symptoms from the debilitating disease.

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Transfusion-Dependent Beta Thalassemia: OTL-300

Orchard Therapeutics, a biotechnology company, recently had the EMA grant priority medicine (PRIME) designation to OTL-3000, a gene therapy approach for the treatment of transfusion-dependent beta thalassemia. This designation accelerates development of treatment that target areas of unmet needs.

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Fanconi Anemia: Ex-Vivo Gene Therapy

Genethon, a non-profit research center, is developing a gene therapy treatment for Fanconi Anemia. Currently, the only treatment for this rare disease is by hematopoietic cell transplant, which can be risky to patients. With the ex-vivo treatment, a vector is delivered in a lab to extracted cells to create more blood stem cells. This treatment has seen encouraging signs and is currently in Phase III of clinical trials.

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Fanconi Anemia: RP-L102

Rocket Pharmaceuticals, a gene therapy company, is working on a treatment called RP-L102 to help patients with Fanconi Anemia. The treatment is currently in Phase I/II clinical trials, and has shown promising results in patients so far.

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Sickle Cell Disease: CRISPR

Vertex Pharmaceuticals is collaborating with CRISPR gene-editing technology to investigate this approach for Sickle Cell Disease and Beta Thalassemia, currently in phase I/II of clinical trials. Gene editing does not need a vector to deliver the functioning gene—instead the correct genetic sequence is delivered directly to the cell.

Editas Medicine is also developing a treatment for Sickle Cell Disease using CRISPR gene-editing technology and is in preclinical study.

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Sickle Cell Disease: Ex-Vivo Gene Therapy

The Dana-Farber Cancer Institute and Boston Children's Cancer and Blood Disorders Center are collaborating on a gene therapy strategy to help patients with sickle cell disease. The investigator-initiated clinical trial uses gene therapy to influence the expression of the BCL11A gene to increase production of fetal hemoglobin.

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Hemophilia: AMT-061

UniQuire, a biotechnology company, is working on developing a gene therapy treatment for hemophilia. Hemophilia is a severe blood clotting disorder. AMT-061 uses a vector to correct a faulty gene, helping increase patients’ clotting activity in their body. The treatment is currently moving on to Phase III clinical trial.

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Hemophilia A and B: SB-525 and SB-FIX

Sangamo Therapeutics, a biotechnology company, is developing gene therapy treatments to help patients with Hemophilia A and Hemophilia B. Both treatments are currently in Phase I/II clinical trial. SB-525 helps patients with Hemophilia A by delivering a copy of the Factor 8 gene via AAV vector to the patient’s liver cells, helping the produce and secrete an important protein to the bloodstream. SB-FIX uses gene editing to permanently insert a new copy of the Factor 9 gene, which also then helps produce and secrete an important protein to enter the bloodstream.

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Hemophilia A: BMN 270

BioMarin, a biotechnology company, is designing a gene therapy treatment for patients with Hemophilia A. This treatment uses a vector to deliver a functional gene that helps create a protein integral to the clotting process. The treatment is currently in Phase III of clinical trials.

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Developing A Treatment

How do clinical trials work? Gene therapies take years to go from theoretical concepts, to preclinical trials, to clinical trials, and, finally, into actual treatments that can improve the lives of patients. Here we learn about the process of developing a treatment.


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