● Xanthine oxidase reported to modulate progression of chronic kidney disease,
diabetic kidney disease, polycystic kidney disease, and other indications ●
CALGARY, Alberta, Aug. 29, 2024 (GLOBE NEWSWIRE) -- XORTX Therapeutics Inc. ("XORTX" or the "Company") (NASDAQ: XRTX | TSXV: XRTX | Frankfurt: ANU), a late-stage clinical pharmaceutical company focused on developing innovative therapies to treat progressive kidney disease, is pleased to report that recent peer-reviewed, independent, published research highlights that genetic factors are linked to the over-expression of xanthine oxidase ("XO") and play a role in several diseases, including kidney disease. These ground-breaking findings further support the Company's approach to treating kidney and other diseases by inhibiting XO.
Xanthine oxidase is an essential enzyme within the uric acid metabolic pathway and is required for the breakdown of purine nucleotides. The breakdown products of XO, including uric acid ("UA") and reactive oxygen species ("ROS"), are released during the enzymatic reaction and may play a detrimental role in the circulatory system and within tissue during disease. XORTX sponsored discoveries in rodent models of polycystic kidney disease ("PKD") implicate over-expression or over-activity of XO as a potentially important target in treating this disease.
Evidence for over-expression of XO in human PKD has not been reported to date, although work by Wang et al. suggests linkage of genetic factors to PKD1. Recently, new emerging discoveries link genetic factors to specific populations and show that higher XO expression is associated with a variety of conditions including hyperuricemia2, sepsis, organ failure and sepsis associated acute respiratory distress syndrome (ARDS)3,4, kidney dysfunction3,4, diabetes5, PKD1,5 and kidney failure6,7. From a mechanistic standpoint, these studies advocate for a precision-medicine approach in which genetic risk variants would guide treatment decisions1.
Commenting on the research, Allen Davidoff, Ph.D., CEO of XORTX, stated, "The combination of pioneering research in autosomal dominant polycystic kidney disease ("ADPKD") sponsored by XORTX and these peer-reviewed, published research papers support our belief that pharmacologic targeting of XO holds enormous therapeutic potential, specifically where increased XO activity is associated with non-diabetic or diabetic kidney diseases. These discoveries highlight an opportunity to develop a personalized therapeutic approach for individuals whose unique genetic factors predisposed them to disease, and the need for xanthine oxidase inhibition to treat those individuals at risk. We believe that XORTX's expertise in developing XO inhibitors, protected by a patent portfolio that anticipated this opportunity, combined with our therapeutic platform is ideally positioned to deliver targeted therapeutics to individuals. Our planned clinical trial in patients with ADPKD will test XORLO, our proprietary formulation of oxypurinol, and will also provide an opportunity to further understand the role of these newly identified genetic factors in individuals with PKD."
References:
Korsmo HW, Emerging roles of xanthine oxidoreductase in chronic kidney disease, Antioxidants, June 2024
Major TJ, et all, Evaluation of the diet wide contribution to serum urate levels: Met-analysis of population based cohorts, BMJ, 363, k3952, 2018
Gao, Li et al., Xanthine oxidoreductase gene polymorphism are associated with high risk of sepsis and organ failure, Respir. Res, 24, 177_2023
Liu H, et al., Genetic variants in XDH are associated with prognosis off gastric cancer in a Chines population, 663, 196, 2013
Wang et al., Genetic susceptibility to diabetic kidney disease is linked to promoter variants of XOR, " The authors identified an expression quantitative trait loci (QTL) in the cis-acting regulatory region of the xanthine dehydrogenase, or xanthine oxidoreductase (XO), a binding site for C/EBPβ, to be associated with diabetes-induced podocyte loss in diabetic kidney disease in male mice. They concluded that certain types of alleles of a gene that controls the expression of xanthine oxidase can be over expressed in CKD, diabetic kidney disease and polycystic kidney disease.
Kudo M et al., Functional Characterization of Genetic Polymorphisms Identified In the Promotor Region of the Xanthine Oxidase Gene, Drug Metab. Pharmacokinet., 25, 599, 2010
Boban M, et al., Circulating purine compound, uric acid, and xanthine oxidase/dehydrogenate relationship in essential hypertension and end stage renal disease., Ren. Fail., 36, 613, 2014
About XORTX Therapeutics Inc.
XORTX is a pharmaceutical company with two clinically advanced products in development: 1) our lead, XRx-008 program for ADPKD; and 2) our secondary program in XRx-101 for acute kidney and other acute organ injury associated with Coronavirus / COVID-19 infection. In addition, XRx-225 is a pre-clinical stage program for Type 2 Diabetic Nephropathy. XORTX is working to advance its clinical development stage products that target aberrant purine metabolism and xanthine oxidase to decrease or inhibit production of uric acid. At XORTX, we are dedicated to developing medications to improve the quality of life and future health of patients. Additional information on XORTX is available at .
For more information, please contact:
Allen Davidoff, CEO adavidoff@xortx.com or +1 403 455 7727 Kim Golodetz, LHA Investor Relations kgolodetz@lhai.com or +1 212 838 3777 | Nick Rigopulos, Director of Communications nick@alpineequityadv.com or +1 617 901 0785 |
Neither the TSX Venture Exchange nor Nasdaq has approved or disapproved the contents of this news release. No stock exchange, securities commission or other regulatory authority has approved or disapproved the information contained herein.
●黄嘌呤氧化酶据报道可调节慢性肾脏病、糖尿病肾脏病、多囊肾病和其他适应症的进展●
卡尔加里,阿尔伯塔省,2024年8月29日(GLOBE NEWSWIRE)——XORTX Therapeutics Inc.("XORTX"或"公司")(纳斯达克:XRTX | TSXV:XRTX | 法兰克福:ANU)是一家专注于开发创新治疗进展性肾脏疾病的临床后期药品公司,很高兴地报道,最近经同行评议、独立、公开发表的研究强调了遗传因素与黄嘌呤氧化酶("XO")的过表达之间的联系,并在多种疾病中发挥作用,包括肾脏疾病。 这些突破性的发现进一步支持公司通过抑制XO来治疗肾脏和其他疾病的方法。
黄嘌呤氧化酶是尿酸代谢途径中的重要酶,用于嘌呤核苷酸的分解。 XO的分解产物,包括尿酸("UA")和活性氧("ROS"),会在酶促反应过程中释放,并在疾病期间在循环系统和组织内发挥不利作用。 XORTX在多囊肾病("PKD")的啮齿动物模型中发现,XO的过度表达或过度活性可能是治疗该疾病的重要靶点。
尚未报道人类PKD中XO的过度表达,尽管Wang等人的研究表明遗传因素与PKD1的联系。最近的新发现将遗传因素与特定人群联系起来,并显示较高的XO表达与多种疾病有关,包括高尿酸血症2、感染、器官衰竭和与感染相关的急性呼吸窘迫综合征(ARDS)3,4、肾功能障碍3,4、糖尿病5、PKD1,5和肾衰竭6,7。从机制上讲,这些研究主张采用个体化治疗方法,遗传风险变异将指导治疗决策。
医药概念中期建议将XORTX Therapeutics公司官方名字替换为中文名字,本文件中不再单独翻译。
在对研究发表评论时,XORTX的首席执行官Allen Davidoff, 博士表示:“由XORTX赞助的关于常染色体显性多囊肾病(ADPKD)的开创性研究以及这些同行评议的、发表的研究论文的组合,支持了我们的观点,即通过药物靶向xanthine oxidase(XO)在非糖尿病肾脏疾病或糖尿病肾脏疾病中增加的XO活性相关联的治疗潜力巨大。这些发现突显了为那些以疾病预设遗传因素的个体开发个性化治疗方法的机会,以及治疗个体风险的黄嘌呤氧化酶抑制剂的需求。我们相信,XORTX在开发XO抑制剂方面的专业知识,加上我们保护这一机会的专利组合,并结合我们的治疗平台,处于理想的位置来为个体提供有针对性的治疗。我们计划在ADPKD患者中进行临床试验,测试我们的独家配方XORLO的氧氧杂离子,也将有机会进一步了解这些新鉴定的遗传因素在PKD患者中的作用。”
参考文献:
Korsmo HW,“Xanthine oxidoreductase在慢性肾脏病中的新兴角色”, 抗氧化剂, 2024年6月
Major TJ, 等. “评估饮食对血清尿酸水平的广泛贡献:基于人群的队列的荟萃分析”, BMJ, 363, k3952, 2018年
Gao, Li等. “黄嘌呤氧化酶基因多态性与高危脓毒血症和器官衰竭的关联”, 呼吸系统研究, 24, 177_2023
Liu H等人在中国人群中发现,XDH基因的遗传变异与胃癌预后有关,2013年,663,196
Wang等人发现,糖尿病肾病的遗传易感性与XOR启动子变异有关,“作者发现某条基因对xanthine氧化酶的表达具有多态性,它是糖尿病肾病中与C/EBPβ结合的负性调控区域上的一个表达定量位点(QTL),与雄性小鼠糖尿病诱导的足细胞丢失相关。他们总结,xanthine氧化酶表达基因的某些等位基因可能在CKD、糖尿病肾病和多囊肾病中过度表达。
Kudo m等人对Xanthine Oxidase基因启动子区域中发现的遗传多态性进行了功能评估,药物代谢和药动学,25,599,2010
Boban m等人对原发性高血压和终末期肾病中循环嘌呤化合物尿酸和xanthine氧化酶/脱氢酶的关系进行了研究,肾功能衰竭,36,613,2014
XORTX是一家制药公司,有两个临床先进产品正在开发中:1)我们的领先XRx-008计划可治疗ADPKD;2)我们的二级计划XRx-101可治疗伴随呼吸道病毒感染的急性肾脏和其他器官损伤。此外,XRx-225是第二型糖尿病性肾病处于临床前阶段。XORTX致力于开发用于改善肾脏疾病患者生活质量和未来健康的药物。有关XORTX的更多信息可访问www.xortx.com。
XORTX是一家药品公司,其有两个临床前进展阶段的产品:1)ADPKD的首席,XRx-008计划; 2)与冠状病毒/ COVID-19感染有关的急性肾脏和其他急性器官损伤的XRx-101二级计划。 另外,XRx-225是2型糖尿病肾病的临床前阶段计划。 XORTX正在努力推进临床发展阶段的产品,以靶向异常的嘌呤代谢和黄嘌呤氧化酶,以降低或抑制尿酸产生。 在XORTX,我们致力于开发药物以提高患者的生活质量和未来健康。 XORTX的其他信息可在该网站上获得。
更多信息,请联系:
首席执行官Allen Davidoff adavidoff@xortx.com或+1 403 455 7727 Kim Golodetz,LHA Investor Relations kgolodetz@lhai.com或+1 212 838 3777 | 通信-半导体主任Nick Rigopulos nick@alpineequityadv.com或+1 617 901 0785 |
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