Research is underway at Indiana University School of Medicine, Riley Children’s Health’s affiliate medical school, to pursue improved therapies for the life-threatening hemophilia diagnosis. The study is funded by the National Heart, Lung, and Blood Institute under a $12 million grant and will seek answers to safer and likely curative treatments for the condition.
Hemophilia, a rare genetic disorder that prevents blood from clotting properly, affects less than 1,000 male patients per year. In severe cases, those with the diagnosis can experience excessive bleeding within the body, particularly in the knees, ankles and elbows. The symptoms damage organs and tissues, and treatment often requires regular replacement of the clotting-infected proteins. Roland Herzog, PhD, professor of immunology at Riley Children’s Foundation, will study a gene therapy approach that will allow the body to make its own clotting factors, thanks to a delivery mechanism called adeno-associated viruses.
“Several companies have taken this forward into clinical trials, and in some of these trials, the patients initially looked like they were cured,” Herzog said. “But what they all have in common is that they need to deliver a lot of the virus in order to get the desired results, and over time, clotting factor levels started to decline. So, it’s clear that we need to further study the biology of this phenomenon.”
Furthermore, hemophilia A, the most common case of hemophilia, causes those affected to not produce enough of the most essential blood-clotting protein, the VIII protein. Alongside Herzog’s approach to find an automatic clot-producing method, he will work amongst national experts to explore hemophilia A in particular.
The nationwide work consists of three gene therapy-focused projects – one to study cellular toxicity and stress in FVIII protein production, a second to study molecular virology and the development of viral vectors that deliver the FVIII-encoding gene, and a third to study the immune system’s role in FVIII production. Key collaborators for the projects include an Indiana University School of Medicine professor, Weidong Xiao, PhD, as well as two others from the Sanford Burnham Prebys Center for Genetic Disorders and Aging Research and Cornell University’s medical school. Their analysis will hopefully lead to lower toxicity rates and improved FVIII production in patients with hemophilia.
“This is an incredibly significant and urgent medical question, and it requires the synergy of multiple groups with different expertise to come together and solve a problem that they wouldn’t be able to solve on their own,” Herzog added. “My hope is that our studies will help the field as a whole move toward curing hemophilia A.”
The pediatric hematology and oncology program at Riley Children’s treats patients to cure complex cases like hemophilia. Learn more about the expert work being accomplished in the annual report.