Small molecule enhancers of detrusor contraction discovered using a functional cell contractility screen as therapeutic candidates for underactive bladder

使用功能性细胞收缩性筛选发现逼尿肌收缩的小分子增强剂作为膀胱活动不足的治疗候选物

• 批准号: 10565844
• 负责人: Ivan Pushkarsky
• 金额: $ 4.16万
• 依托单位: FORCYTE BIOTECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-07 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10565844
• 关键词: Affect; Award; Back; Bladder; CRISPR/Cas technology; Catheterization; Catheters; Cells; Chronic Disease; Chronic Kidney Failure; Collection; Devices; Disease; Enhancers; Impairment; Indwelling Catheter; Manuals; Muscle; Muscle Contraction; Oral; Parents; Patients; Pharmaceutical Preparations; Phenotype; Program Development; Recommendation; Research; Scientist; Smooth Muscle; Therapeutic; Time; Training; Underrepresented Populations; Urethra; Urinary Retention; commercialization; detrusor underactivity; drug development; high throughput screening; novel; parent grant; patient population; pediatric patients; programs; screening; small molecule; therapeutic candidate

Underactive bladder (UAB) / detrusor underactivity (DU), is a chronic disorder arising from impaired contractile function of the bladder in its strength and/or duration, causing prolonged bladder voiding or inability to achieve complete voiding of the bladder at normal time scales. Without treatment, increased urinary retention and back-up will lead to severe and irreversible bladder damage and chronic kidney disease. No available oral medication used in the UAB is completely effective and catherization is often the standard recommendation for managing urinary retention resulting from UAB, even in pediatric patients with idiopathic UAB. This requires the patient either to carry an indwelling catheter and external collection device or more commonly, to self-catheterize four and six times daily, a involving manually guiding a catheter through one’s urethra to the bladder. Forcyte performed the first ever high-throughput screen on bladder cell contractility of 11500 small molecules, identifying two promising hit clusters. In addition to the parent grant aims around phenotypic small molecule discovery, this ADMIN SUPPLEMENT will train a candidate from an underrepresented group in both research and commercialization tasks at Forcyte. In particular, the candidate will aide the company’s commercial expansion into target discovery by working with an expert Sr. Scientist to develop CRISPR techniques for “gain-of-contractile-function” screening.

膀胱活动不足 (UAB) / 逼尿肌活动不足 (DU) 是一种慢性疾病 膀胱收缩功能的强度和/或持续时间受损，导致长时间 膀胱排空或无法在正常时间范围内实现膀胱完全排空。 如果不进行治疗，尿潴留和滞留的增加将导致严重且不可逆转的后果。 膀胱损伤和慢性肾脏疾病。 UAB 中没有可用的口服药物 完全有效，导管插入通常是管理的标准建议 UAB 导致尿潴留，即使是特发性 UAB 儿科患者也是如此。这 要求患者携带留置导管和外部收集装置或更多 通常，每天自行导尿四到六次，需要手动引导导管 通过尿道到达膀胱。 Forcyte 进行了首次高通量筛选 对 11500 个小分子的膀胱细胞收缩性进行研究，确定了两个有希望的命中簇。在 除了围绕表型小分子发现的家长资助之外，该 ADMIN SUPPLMENT 将在研究和研究方面对来自代表性不足群体的候选人进行培训 Forcyte 的商业化任务。特别是，候选人将帮助公司 通过与专家级科学家合作开发目标发现的商业扩展 用于“获得收缩功能”筛选的 CRISPR 技术。