Hope on the Horizon for an Inherited Clotting Disorder
When we sustain a cut or injury, more than a dozen clotting factors, or special proteins circulating in the body, are activated in a cascade to help us stop bleeding. “People born with the genetic disorder hemophilia have insufficient levels of one of these clotting factors, so they bleed for a much longer time than others,” says Greg LaRosa, who leads Pfizer’s Rare Disease Research Unit. About 20,000 people in the U.S. and 400,000 people worldwide are living with hemophilia.
There are two main types of the disease:
Hemophilia A is about four times more common than hemophilia B and occurs when a person inherits a defective gene for clotting Factor VIII, a protein produced in the liver.
Hemophilia B occurs when a person inherits a defective gene for clotting Factor IX, another protein produced in the liver.
Once known as the “royal disease” because it struck descendants of European royal families in the 19th and 20th centuries, hemophilia mainly afflicts males because it’s passed down on the X chromosome. Since females have two X chromosomes, even if they inherit a defective clotting gene from their mother, it’s more likely they will have a working gene from their father. Females can be carriers of the gene and pass the disease onto their children.
Living with Hemophilia
People with hemophilia don’t bleed faster than others, but they bleed for longer than normal, and can bleed spontaneously. The severity of the condition depends on the levels of clotting factor in the blood. About half of patients with hemophilia A have the most severe form of the disease, meaning their blood has less than 1 percent of the normal level of clotting factor found in unaffected people.
In its most serious form, hemophilia may cause people to bleed at least once or twice a week, and often for no apparent reason. Among the most debilitating side effects of the disease is internal bleeding in the joints, which can happen either after an injury, or spontaneously. The pressure from blood filling a joint, such as the knee, ankle or elbow, can cause chronic pain and joint damage similar to symptoms associated with severe arthritis.
What Could Gene Therapy Mean for Patients?
The disease is mainly treated today through infusions of the missing clotting factor. Known as replacement therapy, these treatments are made from human blood or produced in a lab using recombinant DNA technology to produce pure human factor protein. Depending on the severity of their disease, patients undergo replacement therapy by intravenous infusion on a frequent regular schedule (to prevent bleeding) or after a bleeding episode.
With more recent advancements in gene therapy, researchers are hopeful that we may be one step closer to developing novel treatment options for hemophilia patients. Gene therapy is a technology under development for treating diseases caused by a known genetic mutation. The way it works is by introducing corrected copies of missing or defective genes into the body. The new gene is then delivered to the site where it’s needed, in this case the liver, where it instructs the cells to make a correct version of the missing clotting factor which is then secreted into the blood. Typically the gene is delivered using a benign virus — a DNA delivery truck, to use a familiar example. This approach is showing great promise for hemophilia. “Early data shows that we may be entering a new era in treating hemophilia — not by simply replacing the missing factor up to a couple of times a week, but with a single treatment providing a correct version of the gene that may then produce curative levels of factor for life,” says LaRosa.