Factor VII deficiency

Factor VII deficiency

Congenital FVII deficiency is caused by mutations in the F7 gene coding for FVII resulting in low or undetectable FVII levels. Homozygotes develop a hemorrhagic syndrome, where heterozygotes are asymptomatic. Symptoms may differ greatly; some have almost no symptoms while at least 20% of patients experience life-threatening bleedings. Typically, there is a tendency to easy bruising, nose bleeding, menorrhagia, dental and surgical associated bleeding. Also, bleedings can occur in the gut, in muscles or joints, or the brain. Infants with severe factor VII deficiency may develop fatal intracranial hemorrhage within hours or days of birth. Congenital FVII deficiency provides an excellent model for gene transfer as a therapeutic approach because its clinical manifestations occur solely due to the lack of FVII, a protein that circulates in small amounts in the plasma. Unlike other congenital liver disorders, the therapeutic goal for congenital FVII deficiency is an increase of FVII to > 5% of normal which will be sufficient to ameliorate the bleeding tendency, though normal activity levels are the goal of our gene therapy approach. Notably, FVII is structurally and functionally related to human FIX, a molecule for which successful gene therapy has been developed and has been filed for approval at the FDA and EMA with approval expected in 2022.