Innovative Findings Could Enhance Hemophilia A Treatments

Researchers at the Centenary Institute have made significant progress in understanding why some individuals with hemophilia A develop resistance to their standard treatment. Published in the journal Blood Advances, the study reveals that the factor VIII (FVIII) protein, used in therapy, sometimes fails to form all of its stabilizing disulfide bonds. These bonds are crucial for maintaining the proper structure of FVIII. When absent or incomplete, the protein adopts altered shapes that increase the likelihood of triggering an immune response, leading to the production of antibodies that negate the treatment's effectiveness.

Hemophilia A is a genetic disorder characterized by a deficiency in FVIII, a key clotting factor. Patients typically receive regular infusions of FVIII to prevent bleeding episodes. However, some patients' immune systems recognize the infused FVIII as foreign, producing antibodies that block its action. The new research indicates that the structural variability of FVIII, particularly the incomplete disulfide bonds, contributes to this immune recognition.

Lead researcher Dr. Diego Butera explained that their findings showed antibodies from patients preferentially bind to these structurally altered forms of FVIII, impairing treatment effectiveness. This discovery opens avenues for designing more stable versions of FVIII that are less likely to be targeted by the immune system, potentially reducing the incidence of resistance.

Professor Philip Hogg emphasized that engineering FVIII to incorporate more robust disulfide bonds could lead to longer-lasting, more effective treatments. Furthermore, the principles uncovered in this study may apply broadly to other protein-based therapies, highlighting the importance of understanding structural variations in therapeutic proteins for improving safety and efficacy.

This research represents a promising step towards personalized and more effective therapies for individuals with hemophilia A, ultimately aiming to reduce treatment resistance and improve quality of life.

Source: https://medicalxpress.com/news/2025-05-discovery-treatment-people-hemophilia.html