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.