A Mark on Hemophilia

Published: October 28th, 2013

Category: Patient Stories

Taking a closer look at the impact two professors in the Division of Cellular and Molecular Therapy in the Department of Pediatrics are having on hemophilia treatment

Dr. Brad Hoffman

Dr. Brad Hoffman, assistant professor of pediatrics, performing sterile tissue culture work.

People thought Arun Srivastava, Ph.D., and Roland Herzog, Ph.D., were wasting their time studying the adeno-associated virus (AAV). The scientists put everything into researching an agent that does not cause any diseases, results in mild immune responses and was – at the time – considered the most boring virus.

What they discovered, however, was that those same characteristics that made AAV seem boring (it lacks pathogenicity and toxicity, it infects dividing and non-dividing cells of various tissue origins, and it has a very low host immune response and long-term expression) actually made it an ideal candidate for creating viral vectors for gene therapy.

Today, Srivastava’s and Herzog’s contributions to AAV have helped cure a number of human diseases — particularly due to their breakthrough with AAV vectors.

During an early clinical trial, it became obvious that the immune system rejected the traditional vectors used to treat hemophilia (a rare bleeding disorder in which blood does not clot normally). Because the body saw it as a foreign virus, mild liver damage resulted.

When trying to figure out a way to solve this problem, Srivastava and Herzog created a new generation of vectors that the body can tolerate. Moreover, these new vectors are more efficient and are able to provide sustained and therapeutic levels of Factor IX (a protein that allows the blood to clot) at 30-fold lower doses.

Since their discovery, Srivastava and Herzog have published a number of articles in renowned journals, detailing their advances in molecular therapy and how they have eliminated the immune response in the mouse model.

“Not only do we have better vectors now, but they are safer and significantly reduce the cost,” Srivastava said. “Each hemophilic patient costs an average of $100,000 to treat. With the lower dose, we could do the same treatment for $10,000.  Not only is this beneficial for patients but also for production costs.”

During gene therapy, a harmless AAV transmits a working gene into the body. The gene therapy techniques Herzog and Srivastava developed have successfully treated hemophilic mice in their labs. Successful clinical trials in humans have been performed at other institutions.

Prior to their collaboration, there was no basic hemophilia research in the state. With $22 million in funding received for gene therapy, their team has produced a seven-fold return on the investment of $3 million that was generously provided by the Children’s Miracle Network at UF Health Shands Children’s Hospital to create the division.

“We are very fortunate to have Dr. Herzog,” Srivastava said. “It has been a wonderful association. He has helped put us in the spotlight because he has very high visibility and is very well known in the hemophilia community.”

“What drives this research forward is the interdisciplinary approach,” Herzog added. “That’s what attracted me to move here—the interactions between the group of physician scientists and basic scientists with disease-oriented goals and translational research. It has helped me grow scientifically and make a bigger impact on hemophilia research.”

As the two researchers continue to develop the AAV vectors and superior treatment methods, they said they look forward to seeing the fruits of their research—and most of all, better quality of life for hemophilic patients.

“You never know where the next big breakthrough is going to come from—but it tends to come from basic science,” Herzog said. “It’s so important to fund all kinds of research, because if we only had funding for research on diseases, we wouldn’t have better treatment of hemophilia today.”

Srivastava added, “We started out working on a virus that doesn’t do anything, and now it’s become one of the most powerful vectors. I never could have imagined this would amount to anything—and now AAV should be renamed ‘an awesome vector,’ as it is curing a number of human diseases.”

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