Hemophilia


Hemophilia is a genetic disease that prevents blood from clotting properly leading to prolonged internal and external bleeding. There are existing treatments for hemophilia that require lifelong administration, while gene therapy may offer a one-time treatment to address the cause of the disease.

Hemophilia and Gene Therapy

Hemophilia occurs when the genes that are vital to producing clotting factors are faulty. Clotting factors are proteins in blood that help our bodies stop bleeds. Without the ability to effectively stop bleeds, a simple cut or bruise can lead to external bleeds, while internal bleeding inside joints and muscles can damage organs. Although there are 12 defined clotting factors, the two most common types of the disease are hemophilia A and hemophilia B. Hemophilia A is caused by a deficiency in clotting factor VIII, while hemophilia B is due to a deficiency in clotting factor IX.

Gene therapy would deliver a functional version of the faulty gene into a cell, instructing it to produce the missing clotting factor. This delivery is accomplished using a vector, or vehicle, that contains the working gene. Vectors are often derived from viruses because they are capable of entering cells to deliver genetic material, such as a working gene. But don’t worry, all viral genes are removed and the vector is modified to only deliver therapeutic genes into cells.

The vectors are delivered into a person’s liver cells. The liver has a variety of jobs in our body, and one of them is to create different elements in our blood—including clotting factors VIII and IX. By introducing a vector with the functional gene into liver cells, gene therapy instructs the cells to produce and secrete functionally active clotting factors into the bloodstream to help prevent bleeds.

It’s important to note that if a bleed occurs during a clinical trial, the person’s standard treatment would be provided to stop the bleeding. Gene therapy would ideally improve the quality of life for people living with the disease by increasing factor levels and reducing bleed rates.

Pathway to Treatment

Existing Treatments

There are a variety of existing hemophilia treatments, the most common being an infusion to administer clotting factor replacements directly into the bloodstream. Other options include medications, physical therapy, or surgery to repair tissue damage. These treatments are required throughout a person’s entire lifetime to prevent or treat bleeding, which can be time and cost-intensive. Hopefully gene therapy will be a one-time treatment to target the cause of disease, but keep in mind that gene therapy is not a cure, and a person may still get an occasional bleed. However, it may greatly improve the quality of life for a person with hemophilia.

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Gene Editing and Hemophilia

Researchers are also exploring treatment approaches for hemophilia using gene editing to correct clotting factor production. Gene editing seeks the same outcome as gene therapy— to influence how cells produce key proteins or enzymes. However, the goal of gene editing is to remove, disrupt or correct faulty elements of DNA within the gene rather than replace or add a gene. Gene editing uses systems that are highly precise to make this change inside the cell. There are no approved gene editing treatments yet, but many are currently being researched in preclinical study and some are in clinical trials.

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Treatment Pipeline

Investigational gene therapies for hemophilia are currently showing promise in clinical trials. Research and development of these therapeutics is being done by companies such as Sangamo, uniQure, BioMarin, Pfizer, and Spark Therapeutics. To find active and recruiting gene therapy clinical trials, visit the ASGCT Clinical Trials Finder and search for hemophilia in the “diagnosis” field.

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Eligibility

You may be curious how people with hemophilia A or hemophilia B can participate in clinical trials for gene therapy. These trials offer an opportunity to receive an investigational treatment at no cost, while also benefiting the scientific community and others who have the disease. It is important to discuss eligibility, risks, and benefits with the individual’s hematologist or hemophilia treatment center.

To participate in a clinical trial, the individual must meet strict eligibility criteria. A big criteria in the case of a hemophilia treatment is age. Since the liver grows with us from childhood to adulthood, gene therapy trials are currently being conducted in eligible adults with hemophilia. If a child was administered the treatment, the therapy’s beneficial effects could become weaker as their liver grows with age.

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Get Involved

Getting involved with patient advocacy organizations is a great way to connect with other families and patients affected by hemophilia, gather useful resources, and advocate for research. The disease may be rare, but you're not alone.

Hemophilia Federation of America (and check out their Learning Central)

National Hemophilia Foundation

The Coalition for Hemophilia B

World Federation of Hemophilia

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2019

ASGCT Policy Summit

November 4 – 6 | Washington D.C.