A Novel Therapeutic for Liver Fibrosis

描述(申请人提供)：酒精性和非酒精性肝纤维化仍然是肝病学家尚未解决的挑战，因为它可能导致肝硬变和终末期肝病，这是一种危及生命的情况，需要进行肝移植。目前治疗肝纤维化的治疗策略包括改变饮食、生活方式和/或药物以减轻疾病的根本原因。由于肝脏疾病的诊断通常是在显著的疤痕形成之后进行的，因此迫切需要辅助策略来反对导致肝脏疾病的纤维化的分子和细胞程序，并激活基质降解途径。在纤维性肝病模型中，临床前数据的优势说明了自然产生的多肽荷尔蒙Relaxin(H2R)的有益效果。将这些发现转化为临床方案的过程缓慢得令人痛苦，这在很大程度上是因为与商业生产重组人H_2R相关的成本和后勤困难。为了充分利用H_2R的抗纤维化潜力，纽约的Angion Biomedica Corp.和化学和生物制药实验室(CBL，CO)开发了一个商业上可行的H_2R样多肽文库，其成本仅为生产类似数量的重组人H_2R的成本的一小部分。重要的是，我们的初步研究表明，这些新的多肽在体外具有类似H_2R的生物活性。拟议的SBIR第一阶段计划试图从该文库中确定一种主要的抗纤维化候选药物作为治疗肝纤维化的药物。 公共卫生相关性：纤维性肝病在美国是一个主要的健康和社会经济负担。开发一种临床上可行的抗肝纤维化策略对肝病具有重大意义。

DESCRIPTION (provided by applicant): Alcoholic and non-alcoholic liver fibrosis remains an unsolved challenge for the hepatologist as it can lead to cirrhosis and end-stage liver disease, a life-threatening condition that necessitates liver transplantation. Current therapeutic strategies for the treatment of liver fibrosis include changes in diet, life-style and/or medications to alleviate the underlying cause of disease. Since liver disease is typically diagnosed following significant scar formation, adjuvant strategies that oppose the molecular and cellular program of fibrosis that drives liver disease and activate matrix degrading pathways are urgently required. A preponderance of preclinical data in models of fibrotic liver disease speaks to the beneficial effects of the naturally occurring peptide hormone Relaxin (H2R). Translation of these findings into clinical regimen has been painfully slow in large part due to the costs and logistical difficulties associated with commercial production of recombinant human H2R. To fully capitalize on the antifibrotic potential of H2R, Angion Biomedica Corp., NY and Chemical and Biopharmaceutical Laboratories (CBL, CO) have developed a library of H2R-like peptides in commercially viable quantities at a fraction of the cost associated with production of similar quantities of recombinant human H2R. Importantly, our preliminary studies suggest that these novel peptides share H2R-like bioactivity in vitro. The proposed SBIR Phase I program seeks to identify a lead antifibrotic candidate from within this library as a treatment for liver fibrosis. PUBLIC HEALTH RELEVANCE: Fibrotic liver disease is a major health and socioeconomic burden in the United States. Development of a clinically viable antifibrotic strategy against liver disease is of tremendous significance.