Human Gene Therapy Optimized for the Platelet Bleeding Disorder Glanzmann Thrombasthenia

Inherited platelet disorders cumulatively affect roughly 1:20,000 people worldwide. Glanzmann Thrombasthenia (GT) is among these due to defects in genes encoding integrin αIIbβ3 subunits that prevent platelet aggregation, leading to recurrent mucocutaneous bleeding episodes and increased risk of morbidity and mortality from gastrointestinal or intercranial hemorrhage. GT is commonly treated with platelet transfusion, although patients often experience immune-mediated destruction of donor platelets. Antifibrinolytic agents and rFVIIa are also used to treat uncontrolled bleeding but require frequent administration. Allogeneic bone marrow transplant (BMT) has been shown to correct the GT phenotype; however, BMT can cause graft vs host disease and excludes patients without a BMT match. Thus, an effective long-term treatment to control bleeding in human GT is essential.