Exploring the Efficacy of a Proteoglycan Mimic for Treatment of Interstitial Cystitis

探索蛋白多糖模拟物治疗间质性膀胱炎的功效

• 批准号: 8980247
• 负责人: Katherine Stuart
• 金额: $ 19.96万
• 依托单位: SYMIC BIOMEDICAL, INC.
• 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 2016-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8980247
• 关键词: Adsorption; Affect; Affinity; Aftercare; Animals; Back; Balloon Angioplasty; Binding; Biomimetics; Bladder; Bladder Tissue; Blood; Blood Platelets; Blood Vessels; Cells; Chondroitin Sulfates; Chronic; Cicatrix; Clinic; Collagen; Depressed mood; Dermatan Sulfate; Development; Diffusion; Disease; Economic Burden; Endothelial Cells; Environment; Epithelial Cells; Epithelium; Etiology; Evaluation; Extracellular Matrix; Extravasation; Family; Female; Frequencies; GAG Gene; Healed; Hyperplasia; Individual; Interstitial Cystitis; Knowledge; Lead; Medical; Modeling; Morbidity - disease rate; Mus; Nature; Pain; Patients; Peptides; Persons; Phase; Polysaccharides; Preclinical Testing; Prevalence; Proteoglycan; Protocols documentation; Quality of life; Schedule; Sick Leave; Societies; Stream; Surface; Syndrome; Thrombus; Tight Junctions; Tissues; Ulcer; United States; Urine; Waste Products; Water; Woman; Work; aggrecan; cost; design; experience; healing; improved; in vivo; male; men; monocyte; novel therapeutics; prevent; public health relevance; social; solute; suicidal; therapy development

 DESCRIPTION (provided by applicant): Interstitial Cystitis (IC) is a painful syndrome that is chronic in nature. While historic prevalence of IC is conservatively estimated to be 52-200/100,000 females [1], evaluations by Apostolidis and colleagues suggest that the condition affects greater than 2 % of females [2]. Significantly fewer males experience IC, with numbers ranging from 8-41/100,000 individuals [1]. Patients experiencing IC suffer significant morbidities [3]. Quality of life is significantly impacted; patients express difficulties maintaining a regular work schedule, experience challenges in relationships and are often depressed and even suicidal [3]. In the United States, estimates of medical costs for sick leave alone were $428 million in 1987. With respect to filed direct medical claims costs associated with IC as compared to those filed by patients without IC there was an increase of ~$4,200 per person per year in 2002 [3]. Thus, there is a direct medical, social and economic burden on society. This primarily female disease is of unknown etiology; however, there are well-defined pathological changes associated with the bladder wall. The primary function of the intact bladder is to serve as a short-term storage container for urine. The bladder wall must be impermeable to water and waste products while holding the urine to prevent re-adsorption into the blood stream. The lumen of the bladder wall is lined with epithelial cells. The cells form tight junctions with one another and secrete large quantities of polysaccharide on their luminal surface to prevent leakage of urine into the blood vessels within the wall of the bladder. Pathological changes observed in the epithelium of patients with IC include loss of tight junctions between umbrella cells, thinning of the polysaccharide coating, and loss of patches of epithelial cells that can lea to blood in the urine and ulcers in the bladder wall. Loss of bladder impermeability can lead to considerable back and suprapubic pain as solutes migrate into the surround tissue and lead to frequent, painful voiding [4, 5]. Symic Biomedical proposes the development of an improved barrier treatment. By developing therapies that target and bind to the bladder wall, Symic proposes to develop a biomimetic polysaccharide coating that serves as a barrier to solute diffusion into the bladder wall and remains bound for up to one week, thus greatly reducing treatment frequency.

 描述（由申请人提供）：间质性膀胱炎 (IC) 是一种慢性疼痛综合征，虽然保守估计 IC 的历史患病率为 52-200/100,000 名女性 [1]，但 Apostolidis 及其同事的评估表明，该病症影响超过 2% 的女性 [2]，患有 IC 的男性明显较少，人数范围为 8-41/100,000 人。 [1]. 患有 IC 的患者发病率较高 [3]，患者表示难以维持正常生活。 在美国，1987 年仅病假的医疗费用估计就达 4.28 亿美元。与 IC 相关的直接医疗索赔费用相比。与没有 IC 的患者相比，2002 年每人每年增加约 4,200 美元[3]，因此，这种主要是女性的疾病给社会带来了直接的医疗、社会和经济负担。病因学；然而，膀胱壁有明确的病理变化，完整膀胱的主要功能是作为尿液的短期储存容器，同时膀胱壁必须不渗透水和废物。膀胱壁的管腔内排列着上皮细胞，这些细胞彼此紧密连接，并在其管腔表面分泌大量多糖，以防止尿液渗漏。在 IC 患者的上皮中观察到的病理变化包括伞细胞之间紧密连接的丧失、多糖涂层变薄以及可导致膀胱内血液流动的上皮细胞斑块的丧失。膀胱壁的尿液和溃疡。 膀胱不通透性的丧失会导致严重的背部和耻骨上疼痛，因为溶质会迁移到周围组织中并导致频繁的排尿疼痛 [4, 5]。 Biomedical 提议开发一种改进的屏障治疗方法，通过开发靶向并结合膀胱壁的疗法，Symic 提议开发一种仿生多糖涂层，作为溶质扩散到膀胱壁的屏障，并保持结合长达一周。 ，从而大大减少治疗频率。