Peptide Based Therapy for Lung Fibrosis

DESCRIPTION provided by applicant Fibroproliferative illnesses leading to organ fibrosis and failure are responsible for approximately of deaths in developed countries whether idiopathic triggered by environmental factors infections or genetics organ fibrosis results in significant morbidity and mortality Organ fibrosis is responsible for health care costs exceeding $ billion year It is estimated that the number of deaths due to fibrosis is double the number of deaths due to cancer and that organ fibrosis results in significant physical emotional and financial burdens Specifically lung fibrosis can be idiopathic associated with connective tissue diseases or triggered by environmental and occupational exposures such as radiotherapy There are currently no effective therapies to treat existing lung fibrosis and the only option for patients is organ transplantation We have identified a peptide derived from endostatin now called Endopep which exerts anti fibrotic effects in vitro ex vivo and in vivo in pre clinical models of lung fibrosis Endopep was effective whether administered concomitantly with the fibrotic trigger or days after the trigger and appears to reverse fibrosis an effect not seen wit other drugs being evaluated for these illnesses We propose to produce recombinant Endopep by transient expression in whole plants and test the efficacy of the plant made product in our in vitro ex vivo and in vivo pre clinical models of fibrosis We also propose to conduct pharmacokinetic pharmacodynamic biodistribution and early toxicity studies in preparation for an IND application We have assembled a unique team with the expertise to express the peptide in plants conduct the pre clinical testing and complete the early PK PD biodistribution and toxicity studies in order to translate our findings to the clinic PUBLIC HEALTH RELEVANCE Pulmonary fibrosis is a terminal complication of diseases such as idiopathic pulmonary fibrosis IPF and systemic sclerosis SSc We have identified a novel peptide with anti fibrotic activity that is effective at blocking and reversing lung fibrosis We propose to manufacture the peptide in plants test the plant made product for efficacy in our pre clinical models and conduct pharmacokinetic biodistribution and early toxicity studies in preparation for IND application filing