RECIPIENT:  Dr. Ben Matthews
TITLE: PR1P, an inhaled novel short peptide for emphysema
INSTITUTION: Boston Children’s Hospital
DESCRIPTION:  Emphysema is a chronic progressive pulmonary disease characterized by destruction of alveoli leading to impaired lung function that threatens human health worldwide. Disease progression is due in part to dysregulation of the survival factor Vascular Endothelial Growth Factor (VEGF).  Emphysema has no cure: there are no drugs to prevent disease progression or restore lung tissue to health. We recently designed a novel 12 amino-acid peptide, PR1P, that upregulates endogenous VEGF, and that based on recent preliminary data we hypothesize could be used in humans to treat emphysema. Here, we propose to carry out proof of principle testing in animal emphysema models.
Thus, our solution to this problem is an inhaled pharmaceutical (PR1P) that targets and stabilizes endogenous VEGF in the lungs to enhance VEGF signaling and restore lung health. We propose here to characterize the effect of PR1P on emphysema progression in an established 3-week duration murine elastase-induced emphysema model. Mice will be treated with inhaled PR1P (or scrambled peptide), and we will characterize the effects of PR1P on 1) lung mechanics, 2) lung function, and 3) lung architecture during disease progression. Our hypothesis is that PR1P mitigates elastase-induced emphysema progression in murine lungs. Our goal at the completion of this one-year project is to show that PR1P mitigates elastase-induced emphysema in mice. If our hypothesis is correct, then this project plan will provide the proof of principle necessary to support further development of PR1P for use in larger animals and then humans to treat emphysema.