A Novel Therapeutic for Chronic Kidney Disease

产品说明：慢性肾脏病（CKD）仍然是肾病学家面临的一个未解决的挑战，因为它几乎不可避免地导致终末期肾衰竭，这是一种危及生命的疾病，需要肾脏替代治疗。目前用于治疗CKD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。由于肾脏疾病通常在显著的瘢痕形成后被诊断，因此迫切需要对抗驱动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的辅助策略。纤维化肾病模型中的大量临床前数据表明天然存在的肽激素松弛素（H2 R）具有胶原蛋白分解活性。将这些发现转化为临床方案的过程非常缓慢，这在很大程度上是由于与重组人H2 R的商业生产相关的成本和物流困难。为了充分利用H2 R的抗纤维化潜力，Angion Biomedica Corp.，NY和Chemical and Biopharmacological Laboratories（CBL，CO）已经开发了商业上可行量的H2 R样肽文库，其成本是与生产类似量的重组人H2 R相关的成本的一小部分。重要的是，我们的初步研究表明，这些新的肽在体外具有H2 R样生物活性。拟议的SBIR I期计划旨在评估这些H2 R样肽在实验性CKD中的活性。拟议工作的成功完成将使我们能够将前导H2 R样肽纳入全面的SBIR II期计划目标，其中包括开发肽递送的临床最佳策略，在患有共病的CKD模型中评估前导肽，以及作为标准护理的辅助剂和前导肽的安全性/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慢性肾脏疾病纤维化策略具有重大意义。

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.