Peptide Based Therapy for Lung Fibrosis

 描述（由申请人提供）：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人数的45%;无论是特发性、环境因素、感染或遗传引发的器官纤维化，都会导致显著的发病率和死亡率。器官纤维化导致每年超过100亿美元的医疗保健费用。据估计，由于纤维化死亡的人数是死亡人数的两倍。 由于癌症导致的死亡，以及器官纤维化导致显著的身体、情感和经济负担。具体来说，肺纤维化可以是特发性的，与结缔组织相关， 疾病，或由环境和职业暴露（如放射治疗）引发。目前还没有有效的疗法来治疗现有的肺纤维化，并且肺纤维化的唯一选择是肺纤维化。 病人是器官移植。我们已经鉴定了衍生自内皮抑制素的肽，现在称为Endopep，其在肺纤维化的临床前模型中在体外、离体和体内发挥抗纤维化作用。无论是与纤维化触发剂同时给药还是在触发剂后数天给药，Endopep都是有效的，并且似乎可以逆转纤维化，这是其他正在评估的用于这些疾病的药物所未见的效果。我们提出通过在整个植物中瞬时表达来生产重组Endopep，并在我们的体外、离体和体内临床前纤维化模型中测试植物制造的产品的功效。我们还建议开展药代动力学、药效学、生物分布和早期毒性研究，为IND申请做准备。我们组建了一个独特的团队，拥有在植物中表达肽的专业知识，进行临床前测试，并完成早期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.