Workshop Examines Emerging Hemophilia Therapies

A workshop on new bleeding disorders therapies provided insights on improved clotting factors, immune responses to new treatments and gene therapy safety.

Every two years, the National Hemophilia Foundation (NHF) hosts a workshop for the world’s hemophilia experts to share and discuss breakthroughs in bleeding and clotting disorders research and technology. The 10th Workshop on Novel Technologies and Gene Transfer for Hemophilia was co-chaired by Glenn Pierce, PhD, MD, vice president of Biogen Idec Hemophilia in Waltham, Massachusetts, and Thierry VandenDriessche, PhD, of the University of Leuven in Belgium. The organizing committee included Katherine High, MD, of The Children’s Hospital of Philadelphia; Nigel Key, MD, of the University of North Carolina at Chapel Hill; David Lillicrap, MD, of Queen’s University in Ontario, Canada; and Steven Pipe, MD, of the University of Michigan in Ann Arbor. Forty-three scientists presented their findings at the University of North Carolina at Chapel Hill February 5–6, 2010.

A collaborative, optimistic attitude permeated the sessions. “We want to achieve a cure, or we want to achieve long-term correction with the advanced bioengineered products,” VandenDriessche said. “With the progress that has been reported over the past few days, I’m more confident than ever that we will get there.”

While a cohort of biochemists and microbiologists study biochemical details about immune responses to factor VIII, others are contributing new technologies. Researchers in the lab of Friedrich Scheiflinger, PhD, of Baxter BioScience, Biomedical Research Center in Vienna, Austria, are examining the potential of fucoidan, a compound extracted from seaweed, as a component of an oral therapy for bleeding disorders. Fucoidan hampers the body’s inherent anti-clotting actions. Since fucoidans can be a natural part of a person’s diet, there is less concern about adverse immune system reactions.

Another researcher working in the area of oral therapy for hemophilia is Roland Herzog, PhD, of the University of Florida in Gainesville. His team is focusing on the increasing number of people with hemophilia who develop inhibitors, antibodies to therapeutic factor. People with hemophilia B who develop inhibitors are at risk of severe allergic reactions to factor IX (FIX) product, which makes treatment especially difficult. Herzog’s team is developing an orally delivered FIX modified to grow in plant leaves. It has been shown in animal models to promote tolerance to FIX therapy, while substantially lowering the risk of allergic reaction.

Other technologies are making the move from the lab to the clinic. Clinicians reported positive results from clinical trials testing both longer-lasting and faster-acting recombinant FVIIa products, which will benefit people with inhibitors to factors VIII and IX. Both products are nearing the final stages of testing.

While improved recombinant clotting factor products remain an important area of research, the quest for effective and safe gene therapy treatment for hemophilia continues. The challenges of delivering a functional factor-encoding gene to the body without triggering the immune system remain. Yet, innovative approaches arise from seeming roadblocks. VandenDriessche’s research team is investigating an emerging technology involving transposons, groupings of mobile DNA, to combat hemophilia B. The team is working to plug the FIX gene into a super-efficient transposon that could safely deliver the gene to cells that could make FIX. Because this approach doesn’t use a modified virus as a gene delivery vehicle, the expectation is that the immune system response will be less likely to reject the gene containing the FIX blueprint.

As new research discoveries emerge, one fundamental theme remains: patient safety. “It’s necessary that people understand that although there are very safe and efficacious therapies out there, innovation should continue,” Scheiflinger said. “However, safety should not be compromised in favor of patient convenience.