Abstract 19805: Development of a Novel Human Anti-OPG Antibody That Attenuates Experimental Pulmonary Arterial Hypertension

Introduction: Pulmonary arterial hypertension (PAH) is a fatal disease driven by a sustained pulmonary vasoconstriction and progressive vasculopathy leading to right heart failure. Current therapies for PAH relieve symptoms primarily through vasodilatory mechanisms but do not provide a cure. Osteoprotegerin (OPG) is increased within serum and pulmonary vascular lesions of patients with idiopathic PAH, and induces pulmonary artery smooth muscle cell proliferation and migration. Additionally, OPG-/- mice are protected from developing SuHx-induced PAH. Hypothesis: Treatment with a novel human anti-OPG antibody will slow/stop disease progression, or regress established PAH. Methods: High affinity anti-human OPG monoclonal antibodies were generated using the KyMouse™ system. Four novel anti-OPG antibodies with distinct profiles of TRAIL and RANKL binding inhibition, and cross-reactivity to rat were identified. Antibodies were tested (3 mg/kg/week, i.p.) for their ability to prevent PAH in the monocrotaline (mc...