Peptide Based Therapy for Lung Fibrosis

 描述(申请人提供)：在发达国家，导致器官纤维化和衰竭的纤维增生性疾病约占死亡的45%；无论是由环境因素、感染或遗传因素引发的特发性疾病，器官纤维化都会导致显著的发病率和死亡率。器官纤维化是每年超过100亿美元的医疗费用的原因。据估计，死于纤维化的人数是死于 癌症导致的死亡，以及器官纤维化导致重大的身体、情感和经济负担。具体地说，肺纤维化可为特发性，与结缔组织相关。 疾病，或由环境和职业暴露引发的，如放射治疗。目前还没有有效的治疗方法来治疗现有的肺纤维化，唯一的选择是 患者是器官移植。我们已经确定了一种来源于内皮抑素的多肽，现在称为Endoep，在肺纤维化的临床前模型中，它在体外、体外和体内都发挥着抗纤维化的作用。无论是与纤维化触发同时使用还是在触发几天后使用，恩多普都是有效的，而且似乎可以逆转纤维化，这一效果在其他药物对这些疾病的评估中是看不到的。我们建议通过在整个植物中瞬时表达来生产重组内毒素，并在我们的体外、体外和体内临床前纤维化模型中测试植物制成的产品的有效性。我们还建议进行药代动力学、药效学、生物分布和早期毒性研究，为IND的应用做准备。我们已经组建了一个独特的团队，拥有在植物中表达多肽的专业知识，进行临床前测试，并完成早期的PK、PD、生物分布和毒性研究，以便将我们的发现转化为临床。

 DESCRIPTION (provided by applicant): 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.