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Researcher Profile: Roland Herzog, PhD

Researcher aims to use gene therapy to correct factor IX deficiency

By Sarah Aldridge | 08.24.2010
Originally Published August 2010

Roland Herzog

HemAware is conducting a series of interviews with researchers who have received awards from the National Hemophilia Foundation (NHF) to pursue their research interests. This interview was conducted with Roland Herzog, PhD, associate professor of pediatrics, microbiology and molecular genetics at the University of Florida, Gainesville. His lab conducts research on the use of gene therapy for hemophilia, primarily hemophilia B, or factor IX (FIX) deficiency. It is also pursuing various methods of inducing immune tolerance to prevent the formation of inhibitors, antibodies to factor products.

What drew you to this field? What was your initial interest in this field of research?

Although Herzog’s graduate research and PhD at Auburn University in Alabama in the mid-1990s were in microbiology, he had set his sights on what was then a relatively new field: gene therapy. Postdoctoral research at The Children’s Hospital of Philadelphia (CHOP) with Katherine A. High, MD, hematology researcher and William H. Bennett Professor of Pediatrics at the University of Pennsylvania School of Medicine, led to Herzog’s career shift. “This was in 1996—so 14 years later, I am still working on developing therapies for hemophilia.”

Where were you in your career when you received the NHF Career Development Award?

Herzog won the award in 2000 for the project “Immunology of Liver-Derived Expression of Factor IX from AAV Vectors.” The grant started the same day he began his appointment as assistant professor of pediatrics at the University of Pennsylvania.

How did you use the grant?

“I used it to start my own independent research in gene therapy for hemophilia,” Herzog says.

Did the research NHF funded through the Career Development Award assist in advancing your own position at your research institution/hospital? Or did it serve as a building block to further your career or research in hemophilia?

Herzog says the award was “tremendously helpful” in fulfilling both needs. “Because it paid a large portion of my salary, it freed up money from what I was provided for a startup package to hire help in the lab and get the projects going. There was no delay. I could dive into those research programs without having to worry about having enough money.”

Are you still engaged in coagulation or bleeding disorders research specifically?

“Yes, 90% or more of the research I’m doing is on hemophilia.”

How does/will your research have an impact on the clinical aspects of patient care?

Herzog has focused primarily on gene therapy to correct FIX deficiency. He has had success using the adeno-associated virus, which is noninfectious to humans, as the vehicle to carry the corrected FIX gene into the body. A 2009 study with collaborators from Auburn and CHOP provides promise. “We showed eight years of correction in these animals. That was very reassuring that this can work for a long time.”

Several clinical trials of the AAV system are being conducted on human subjects. “We laid the foundation for the development of gene therapy—not just myself, but a large group of people,” Herzog says. “That, in the long run, is going to change how patients are treated.”

The other main pursuit of Herzog’s lab is to outwit the body’s production of inhibitors. He is using the liver to induce tolerance to factor proteins. “If you introduce the FIX gene using AAV into the liver of animals, when the hepatocytes [liver cells] produce the FIX, it can induce immune tolerance to the factor product.” The liver gene transfer approach is now being used in several clinical trials.

The drug rapamycin suppresses the immune system. Given to transplant recipients to prevent their body’s rejection of the donor organ, it is being tested in Herzog’s lab for use in hemophilia. “We developed an immune tolerance protocol using rapamycin, an immune modulatory drug. If you optimize administration of rapamycin with the clotting factor, then you can achieve immune tolerance that way,” Herzog says. Its use in mice with hemophilia A and B has been successful, he adds.

Another way of achieving immune tolerance could be through the oral delivery of a medication. Herzog’s team is working with Henry Daniell, PhD, a plant biologist who has developed plants that manufacture FIX in their leaves. The leaves are ground and fed to mice with hemophilia B before giving them FIX. “When we fed these mice the transgenic material in the leaves, it suppressed inhibitor formation,” he says. Then the mice were given clotting factor. “The immune response that you get to the leaf material suppresses the response to the clotting factor, so you don’t get the inhibitors and the anaphylactic (severe allergic) reaction.” The next step, Herzog says, is to test the approach in mice with hemophilia A and, eventually, people.

What career goals do you have for the future?

Herzog is not looking ahead to the next position, but rather to what he can achieve through his research. “There are two things I would like to accomplish—one is to see gene therapy for hemophilia become a reality, and two, I would like for our immune tolerance protocol to become a reality.”

Where do you see bleeding disorders research going?

Although gene therapy has slowed, Herzog has confidence in its eventual success. “I think it will be the choice of treatment in the future,” he says. One day, he predicts, hematologists will be able to determine which patients will develop inhibitors and use medications to prevent or reverse the inhibitor. “If these immune modulations become reality, I think we will have more cost-effective treatments.”

Drugs with longer half-lives are also on the horizon. “You won’t have to infuse these as frequently,” he says. “You will get more prolonged therapy with what you’re injecting.”

When you’re not working, how do you “escape” from your work?

Herzog spends much of his free time writing grants for research funds. Beyond the lab’s walls, though, is someone who demands his time and attention—his 2-year-old son, Christopher. “My wife is also busy working for a biotech company, so outside work, we’re consumed with the little one. On the other hand, it’s a lot of fun to see him grow and learn.” A new swimming pool helps the family cope with Florida’s hot, humid weather. Most of the family’s travel plans involve sharing Christopher with grandparents in New Jersey and Germany.

There is one diversion Herzog saves for solo trips—a 1989 Pontiac Turbo Trans Am. “I drive it on Sunday afternoon, if I get to it,” he says. But it is a guilty pleasure. “My wife sometimes complains about the expense of that hobby,” he adds with a chuckle.