Safety Study of Gleevec® in Children With Pulmonary Hypertension

Idiopathic pulmonary artery hypertension (IPAH) is a rare but progressive disease in children and adults with a very high mortality from right heart failure. Platelet derived growth factor (PDGF) has been implicated in the pulmonary artery remodeling and vascular proliferation that is a pathologic hallmark of IPAH. Animal and clinical data support the hypothesis that activation of the PDGF receptor is critical in the development of IPAH, and inhibition of the PDGF signaling pathways may be a potential therapeutic target. Gleevec is a tyrosine kinase inhibitor developed for treatment of certain cancers and inhibits the PDGF receptor. Animal and preliminary clinical data suggest that Gleevec can reverse vascular remodeling and improve right heart failure. A small clinical trial for adults with IPAH is ongoing in Europe, but there are no trials in children where the disease has a worse prognosis. This project is a phase II, single dose pilot study to generate the hypothesis that activation of the PDGF receptor is critical in the development of IPAH, and inhibition of the PDGF signaling pathways is a potential therapeutic target. Five patients between the ages of 8 yr to 18 yr with severe IPAH will be recruited nationally, for a 6 month trial of Imatinib. The Specific Aim of this study is to collect preliminary data on the safety and efficacy of Gleevec in children with IPAH. Results from this study are needed to develop a larger, multi-center trial to determine the efficacy and therapeutic impact of Gleevec in children with IPAH. The long term goal of this work is to develop novel therapeutic strategies for treatment of IPAH in children. This translational study of the inhibition of the PDGF receptor in children with IPAH could provide insights into the etiology of IPAH and have a major impact on the development of new treatment strategies for both children and adults with pulmonary artery hypertension from multiple origins.