O impacto da terapia gênica na saúde musculoesquelética de pacientes com hemofilia grave

Abstract

Hemophilia is an X-linked hereditary bleeding disorder that presents with absent or insufficient production of factor VIII (FVIII), in hemophilia A, or factor IX (FIX), in hemophilia B. Patients with severe hemophilia (FVIII or FIX < 1%) have recurrent joint bleeding (ankles, knees and elbows), which lead to progressive arthropathy.The best approach to prevent musculoskeletal complications is to prevent hemarthroses, usually with prophylactic replacement of FVIII or FIX concentrates. This treatment requires frequent intravenous infusions and does not guarantee complete control of hemorrhages. In this context, gene therapy is a transformative therapy, with the potential to improve or even normalize hemostasis, with just a single infusion. This prospective study aims to evaluate the impact of gene therapy on the musculoskeletal health of patients with hemophilia A. For this, we analyzed post-gene therapy FVIII expression along with clinical and image evaluation of the musculoskeletal system. Furthermore, the bleeding frequency, the consumption of FVIII concentrate and the musculoskeletal-related biomarkers profile were also assessed, both before and after gene therapy.In this analysis, we included patients with severe hemophilia A who underwent gene therapy with valoctocogene roxaparvovec (AAV5-hFVIII-SQ), at the dose of 6x10 13 vg/kg,