The Truth About Gene Therapy

If you have hemophilia and you’ve been hoping for a cure, there’s good news and bad.

The bad news: Unfortunately, a cure isn’t just weeks or months away.

But here’s the good news: through gene therapy, researchers are closer than ever before.

While doctors have long known how to manage hemophilia, researchers at institutions such as the Aflac Cancer Center and Blood Disorders Service of Emory University and Children’s Healthcare of Atlanta are both confident and optimistic that they know how to cure the disease.

“We’ve cured mice many different ways,” says Trent Spencer, Ph.D., Director of Aflac’s Gene Therapy Laboratory and Assistant Professor of Pediatrics at Emory University School of Medicine.

“We now routinely cure mice of hemophilia,” says Spencer. “Getting from a mouse to a human, however, is a massive step and that is what we’re trying to do now.”

Gene therapy is an experimental technique that allows doctors to insert a healthy copy of a mutated (bad) gene or even a new gene into a person’s cells to prevent or treat a disease. In the decade that researchers have been working on this technique, results have been both encouraging and frustrating.

“It has taken us a long time to understand how to use genes as therapy,” Spencer explains, but adds that research efforts are improving every year. “Some initially thought that once the gene defect was identified, correcting it would be relatively easy, but we now understand the complexities involved in the gene transfer process. Now we can go back and hopefully increase the effectiveness of our gene transfer systems.”

Gene therapy research got off to a quick start but then seemed to skid to a halt. Although research appeared to slow, in reality a massive effort was underway in laboratories around the world aimed at better understanding the outcomes of the initial gene therapy clinical trials. And the research efforts and initial clinical trials have been extremely fruitful, says Spencer. “We are now incorporating the information learned in the past decade into new gene therapy treatments for hemophilia A,” he says.

Hemophilia A, the most common severe hereditary bleeding disorder, affects about one in 5,000 males. It is caused by a mutation in the gene that produces a blood clotting factor called Factor VIII. In most cases, there is a family history of hemophilia, but in about 30 percent of cases there is no family history and the illness is caused by a spontaneous mutation of the Factor VIII gene that prevents production of the critical protein.

Gene therapy could in theory be used to use a virus – one that has been rendered harmless, of course – to deliver replacement Factor VIII genes.

For example, Spencer and his team are planning to implant Factor VIII genes into the bone marrow of patients using a genetically engineered form of the human immunodeficiency virus (HIV).

The treatment being developed by Spencer and his colleagues could be done in a day as an outpatient procedure and the cells with the transplanted gene could continue to make Factor VIII for the lifetime of the patient. The group plans to meet with the US Food and Drug Administration later this year to discuss clinical trials using the new approach.

Spencer and his team are not the only researchers studying how gene therapy can improve the lives of patients with hemophilia around the world.

“This is an international disease with an international research effort,” says Dr. M. Ian Phillips, Keck Graduate Institute’s Norris Professor of Applied Life Sciences, who is investigating whether inserting other gene factors, such as Factor VII, can make a difference.

Phillips’s research is focusing on bleeding in battlefield injury. He has developed a gene switch that turns on Factor VII when oxygen levels in the blood fall, as happens in bleeding blood vessels. The project, supported by the US Army, is designed to help soldiers in combat who suffer multiple bleeding injuries, both internal and external, that are not accessible to bandages or other treatments.

“Twenty percent of fatalities occur in combat due to loss of blood,” Phillips says, “and where wounded soldiers cannot be evaluated quickly they need an automatic switch to turn on Factor VII to stop the bleeding.” Phillips has also modified genes in stem cells to deliver lifesaving proteins.

Though medical research is both costly and time-consuming (it can take years to go through the clinical trial process), the real issue when it comes to gene therapy, says Phillips, is biology. “Why does something work in animals but not in humans?” he asks.

It’s no consolation, of course, but researchers are running into the same problems with other diseases, such as diabetes, cancer, and Alzheimer’s. “It’s hard to simulate in the lab what biology does for us naturally,” says Phillips.

“But the message is one of hope,” he adds. “Gene therapies are advancing because they are the best solution to certain problems. Science builds on itself and that means we are closer to new gene therapies than ever before.”