Fibroproliferative illnesses leading to organ fibrosis and failure are responsible for approximately 45% 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 $10 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.
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.
|Watanabe, Tomoya; Nishimoto, Tetsuya; Mlakar, Logan et al. (2017) Optimization of a murine and human tissue model to recapitulate dermal and pulmonary features of systemic sclerosis. PLoS One 12:e0179917|