Date
Time
Speakers: Lindsey George, MD; John Morris, PhD; Bill Maurits
This session of the Research Journal Club will focus on gene therapy. Gene therapy for hemophilia A is now commercially available in some countries. While early patient data show a modest reduction in disease severity, current FVIII gene therapies using viral delivery have not yet maintained consistent desired results year after year. This session will explore current work in Dr. Lindsey George’s laboratory at the Children’s Hospital of Philadelphia to use mechanisms of FVIIIa inactivation to engineer enhanced transgenes for hemophilia A gene therapy.
John Morris, PhD
Dr. John Morris is a NHLBI/NIH T32 trainee in hemostasis and thrombosis at the University of Pennsylvania and a postdoctoral fellow at the Children’s Hospital of Philadelphia in Dr. Lindsey George’s lab. His research focuses on defining the biochemistry of activated factor VIII inactivation and exploiting this understanding to engineer gain-of-function clotting factors resistant to inactivation to improve translational applications in hemophilia gene therapy. Additionally, his work aims to develop comprehensive animal models of hemostasis to adequately assess the prothrombotic risk associated with enhanced transgenes that bypass regulatory pathways.
Lindsey George, MD
Dr. George is an assistant professor of pediatrics at the Perelman School of Medicine at the University of Pennsylvania and director of clinical in vivo gene therapy at the Children’s Hospital of Philadelphia. Her laboratory studies the molecular basis of coagulation with a focus on mechanisms that regulate factor VIII/VIIIa cofactor function to improve understanding of associated disease states of deficiency, hemophilia A, or excess function with associated thrombosis. Ongoing studies in her group aim to exploit their biochemical insights of FVIII function to develop novel gene-based therapies for hemophilia A. Dr. George previously led early-phase, adeno-associated virus (AAV) mediated gene transfer trials for hemophilia A and B. Dr. George is a member of the board of directors of the American Society of Gene and Cell Therapy and participates in multiple national and international professional societies for hemostasis and gene therapy research.
Bill Maurits
Bill Maurits is a 53-year-old man with hemophilia B who’s lived through the entire evolution of hemophilia treatment, including a gene therapy trial that changed his life. He’s a devoted husband and proud dad who loves hitting the road with his family, rocking out at concerts with his wife, getting his hands dirty restoring classic cars, and trying to keep up with his 13-year-old son in backyard sports and Taekwondo (though his son is starting to give him a run for his money). Bill brings humor, resilience, and real-life perspective to every audience he meets.
Summary of Webinar
On September 17th, 2025, the National Bleeding Disorders Foundation (NBDF) and the Hemostasis and Thrombosis Research Society (HTRS) hosted a special webinar as part of a new four-part Research Journal Club Series. This exciting event brought together researchers, doctors, and community members to talk about an important topic: New Gene Therapy Treatments.
Why This Matters
This conversation brings together people living with a bleeding disorder, researchers, and clinicians to share the latest advances, real-world impact, and ongoing challenges of gene therapy. These discussions help everyone involved better understand new treatments, set realistic expectations, and identify gaps—like who can benefit, long-term safety, and next research steps. Most importantly, it ensures that patient and family voices guide research and care decisions, leading to more effective, equitable, and meaningful progress for the entire bleeding disorders community.
What the Experts Shared
Overview of Gene Therapy for Hemophilia
Gene therapy for hemophilia is an exciting area of research that aims to help the body make its own clotting factor, which people with hemophilia lack. There are two main approaches:
- In vivo: The most common method, where the therapy is given directly to patients, using special carriers (called AAV vectors) to deliver working genes into liver cells.
- Ex vivo: Involves modifying stem cells outside the body and then returning them to the patient, with early studies showing promise.
Recently Approved Therapies
There are three FDA-approved gene therapies for hemophilia, delivered through an IV infusion:
- Hemgenix for hemophilia B and Roctavian for hemophilia A are available commercially.
- These treatments can help the body produce clotting factor and may reduce and/or eliminate bleeding episodes.
How Gene Therapy Works
Most approved therapies use AAV vectors. AAV is a harmless virus modified to carry the new gene but not cause illness. Scientists remove its viral DNA and insert the gene for the missing clotting factor (either factor VIII or IX). Once infused, the gene instructs liver cells to make the needed clotting factor, which helps prevent bleeds.
Results and Challenges
Hemophilia B: Gene therapy has led to stable clotting factor levels for over ten years, in some cases, greatly reducing annual bleeding.
Hemophilia A: The therapy works, but some studies show a drop in factor VIII levels over time while others have shown stable FVIII levels for multiple years at low levels of FVIII. Research is ongoing for more durable results.
Researchers are exploring ways to improve the function of factor VIII protein and use safer, lower doses of viral vectors.
Next Steps and Future Research
New types of gene therapy, such as gene editing and base editing, aim to correct tiny genetic errors or boost clotting factor function for longer-lasting effects. These new methods may be helpful for some but still need more study and are not yet available clinically.
Another important future goal is making gene therapy safe and effective for children; current treatments focus on adults.
Lived Experience: Patient Story
A Lived Experience Expert (LEE) named Bill Maurits shared that gene therapy dramatically changed his life. After decades of frequent hospital visits, bleeding episodes, and joint pain, he received gene therapy in 2016 and was able to go more than two years without needing an infusion. He is now far more active, able to exercise and participate in family activities, and even earned a black belt in taekwondo. Bill emphasized the importance of honest conversations with healthcare teams and the benefits of being well-informed and connected to resources.
Current Challenges and Considerations
- Not everyone is eligible for current gene therapies—pre-existing immunity to the viral carrier (AAV) can prevent treatment. Research is ongoing to overcome this barrier.
- More studies are needed for children and for those with different genetic variations of hemophilia.
- Updated information is often released, so staying connected to trusted resources—like NBDF and healthcare teams—is important for patients and families.
- You can find research opportunities through the NBDF website, your local hemophilia treatment center (HTC), or clinicaltrials.gov.