Peptide Based Therapy for Lung Fibrosis

肺纤维化的肽疗法

• 批准号: 9330907
• 负责人: Carol A. Feghali-Bostwick
• 金额: $ 74.31万
• 依托单位: NOVICI BIOTECH, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9330907
• 关键词: Biodistribution; Biological Assay; Bleomycin; Cause of Death; Cessation of life; Clinic; Clinical Trials; Collagen; Collagen Type XVIII; Complication; Connective Tissue Diseases; Data; Dermal; Developed Countries; Developing Countries; Disease; Drug Kinetics; Early Diagnosis; Emotional; Endostatins; Environmental Risk Factor; Environmental and Occupational Exposure; Extracellular Matrix; Failure; Fibronectins; Fibrosis; Genetic; Goals; Hamman-Rich syndrome; Health Care Costs; Homeostasis; Human; Hydroxyproline; In Vitro; Infection; Insulin-Like Growth Factor Binding Protein 3; Interstitial Collagenase; Lead; Lung; Lung Transplantation; Malignant Neoplasms; Messenger RNA; Metabolic; Metabolism; Morbidity - disease rate; Mus; Oral; Organ; Organ Transplantation; Organ failure; Patients; Peptides; Pharmaceutical Preparations; Pharmacodynamics; Phase; Plants; Pre-Clinical Model; Preparation; Production; Pulmonary Fibrosis; Radiation therapy; Recombinants; Skin; Stromelysin 1; Systemic Scleroderma; Tenascin; Testing; Therapeutic; Therapeutic Effect; Thick; Toxic effect; Transforming Growth Factor beta; Translating; Urokinase; Wit; Wound Healing; base; chemical synthesis; commercialization; connective tissue growth factor; cost; effective therapy; efficacy testing; in vitro activity; in vivo; indium-bleomycin; intraperitoneal; metabolic abnormality assessment; mortality; novel; pre-clinical; prevent; public health relevance; research clinical testing; response; synthetic peptide

 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.

 描述（由申请人提供）：导致器官纤维化和衰竭的纤维增生性疾病导致发达国家约 45% 的死亡；无论是由环境因素、感染还是遗传引发的特发性，器官纤维化都会导致显着的发病率和死亡率。据估计，每年因纤维化而死亡的人数是其两倍。 癌症导致的死亡，器官纤维化会导致严重的身体、情感和经济负担。具体来说，肺纤维化可能是特发性的，与结缔组织有关。 疾病，或由环境和职业暴露（例如放射治疗）引发。 目前尚无有效的疗法来治疗现有的肺纤维化，也是治疗肺纤维化的唯一选择。 我们已经鉴定出一种源自内皮抑素的肽，现在称为 Endopep，它在体外、离体和体内的肺纤维化模型中发挥抗纤维化作用，无论是否与纤维化触发或触发后几天，似乎可以逆转纤维化，这是其他正在评估这些疾病的药物所未见的效果，我们建议通过在整个植物中瞬时表达来生产重组 Endopep。我们还建议在体外、离体和体内纤维化临床前模型中测试植物产品的功效，为 IND 申请做准备。我们组建了一支独特的团队，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，以便将我们的研究结果转化为临床。