A Novel Therapeutic for Chronic Kidney Disease

描述：慢性肾脏疾病(CKD)仍然是肾科医生尚未解决的挑战，因为它几乎不可避免地导致终末期肾功能衰竭，这是一种危及生命的疾病，需要肾脏替代治疗。目前治疗慢性肾脏病的治疗策略包括改变生活方式和/或药物以减轻疾病的根本原因。由于肾脏疾病通常是在显著的瘢痕形成后被诊断出来的，因此迫切需要辅助策略来反对导致肾脏疾病的纤维化的分子和细胞程序，并激活基质降解途径。纤维性肾脏疾病模型中的大多数临床前数据表明，自然产生的多肽激素松弛素(H2R)具有胶原分解代谢活性。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第一阶段计划旨在评估这些H2 R样肽在实验性CKD中的活性。这项拟议工作的成功完成将使我们能够将一种类似于过氧化氢受体的铅多肽纳入全面的SBIR第二阶段计划，该计划的目标包括开发多肽递送的临床最佳策略，在合并疾病的慢性肾脏病模型中评估铅多肽，并作为标准护理的辅助以及铅多肽的安全性/毒理学分析。 公共卫生相关性：慢性肾脏疾病是美国的主要健康和社会经济负担。开发一种临床上可行的抗纤维化治疗慢性肾脏疾病的策略具有重大意义。

DESCRIPTION: Chronic kidney disease (CKD) remains an unsolved challenge for the nephrologist, as it almost inevitably leads to end-stage renal failure, a life-threatening condition that necessitates renal replacement therapy. Current therapeutic strategies for the treatment of CKD include changes in life-style and/or medications to alleviate the underlying cause of disease. Since renal disease is typically diagnosed following significant scar formation, adjuvant strategies that oppose the molecular and cellular program of fibrosis that drives renal disease and activate matrix degrading pathways are urgently required. A preponderance of preclinical data in models of fibrotic renal disease speaks to the collagen catabolyzing activity 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 anti-fibrotic 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 evaluate the activity of these H2R-like peptides in experimental CKD. Successful completion of the proposed work will enable us to enter a lead H2R-like peptide into a comprehensive SBIR Phase II program goals for which include developing clinically optimal strategies for peptide delivery, evaluation of lead peptide in CKD models with co-morbid disease and as adjuvant to standard-of-care and safety/toxicology profiling of lead peptide. PUBLIC HEALTH RELEVANCE: Chronic kidney disease is a major health and socioeconomic burden in the United States. Development of a clinically viable antifibrotic strategy against chronic kidney disease is of tremendous significance.