● 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.
●黃嘌呤氧化酶據報道可調節慢性腎臟病、糖尿病腎臟病、多囊腎病和其他適應症的進展●
卡爾加里,阿爾伯塔省,2024年8月29日(GLOBE NEWSWIRE)——XORTX Therapeutics Inc.("XORTX"或"公司")(納斯達克:XRTX | TSXV:XRTX | 法蘭克福:ANU)是一家專注於開發創新治療進展性腎臟疾病的臨床後期藥品公司,很高興地報道,最近經同行評議、獨立、公開發表的研究強調了遺傳因素與黃嘌呤氧化酶("XO")的過表達之間的聯繫,並在多種疾病中發揮作用,包括腎臟疾病。 這些突破性的發現進一步支持公司通過抑制XO來治療腎臟和其他疾病的方法。
黃嘌呤氧化酶是尿酸代謝途徑中的重要酶,用於嘌呤核苷酸的分解。 XO的分解產物,包括尿酸("UA")和活性氧("ROS"),會在酶促反應過程中釋放,並在疾病期間在循環系統和組織內發揮不利作用。 XORTX在多囊腎病("PKD")的齧齒動物模型中發現,XO的過度表達或過度活性可能是治療該疾病的重要靶點。
尚未報道人類PKD中XO的過度表達,儘管Wang等人的研究表明遺傳因素與PKD1的聯繫。最近的新發現將遺傳因素與特定人群聯繫起來,並顯示較高的XO表達與多種疾病有關,包括高尿酸血癥2、感染、器官衰竭和與感染相關的急性呼吸窘迫綜合徵(ARDS)3,4、腎功能障礙3,4、糖尿病5、PKD1,5和腎衰竭6,7。從機制上講,這些研究主張採用個體化治療方法,遺傳風險變異將指導治療決策。
醫藥概念中期建議將XORTX Therapeutics公司官方名字替換爲中文名字,本文件中不再單獨翻譯。
在對研究發表評論時,XORTX的首席執行官Allen Davidoff, 博士表示:「由XORTX贊助的關於常染色體顯性多囊腎病(ADPKD)的開創性研究以及這些同行評議的、發表的研究論文的組合,支持了我們的觀點,即通過藥物靶向xanthine oxidase(XO)在非糖尿病腎臟疾病或糖尿病腎臟疾病中增加的XO活性相關聯的治療潛力巨大。這些發現突顯了爲那些以疾病預設遺傳因素的個體開發個性化治療方法的機會,以及治療個體風險的黃嘌呤氧化酶抑制劑的需求。我們相信,XORTX在開發XO抑制劑方面的專業知識,加上我們保護這一機會的專利組合,並結合我們的治療平台,處於理想的位置來爲個體提供有針對性的治療。我們計劃在ADPKD患者中進行臨床試驗,測試我們的獨家配方XORLO的氧氧雜離子,也將有機會進一步了解這些新鑑定的遺傳因素在PKD患者中的作用。」
參考文獻:
Korsmo HW,「Xanthine oxidoreductase在慢性腎臟病中的新興角色」, 抗氧化劑, 2024年6月
Major TJ, 等. 「評估飲食對血清尿酸水平的廣泛貢獻:基於人群的隊列的薈萃分析」, BMJ, 363, k3952, 2018年
Gao, Li等. 「黃嘌呤氧化酶基因多態性與高危膿毒血癥和器官衰竭的關聯」, 呼吸系統研究, 24, 177_2023
Liu H等人在中國人群中發現,XDH基因的遺傳變異與胃癌預後有關,2013年,663,196
Wang等人發現,糖尿病腎病的遺傳易感性與XOR啓動子變異有關,“作者發現某條基因對xanthine氧化酶的表達具有多態性,它是糖尿病腎病中與C/EBPβ結合的負性調控區域上的一個表達定量位點(QTL),與雄性小鼠糖尿病誘導的足細胞丟失相關。他們總結,xanthine氧化酶表達基因的某些等位基因可能在CKD、糖尿病腎病和多囊腎病中過度表達。
Kudo m等人對Xanthine Oxidase基因啓動子區域中發現的遺傳多態性進行了功能評估,藥物代謝和藥動學,25,599,2010
Boban m等人對原發性高血壓和終末期腎病中循環嘌呤化合物尿酸和xanthine氧化酶/脫氫酶的關係進行了研究,腎功能衰竭,36,613,2014
XORTX是一家制藥公司,有兩個臨床先進產品正在開發中:1)我們的領先XRx-008計劃可治療ADPKD;2)我們的二級計劃XRx-101可治療伴隨呼吸道病毒感染的急性腎臟和其他器官損傷。此外,XRx-225是第二型糖尿病性腎病處於臨床前階段。XORTX致力於開發用於改善腎臟疾病患者生活質量和未來健康的藥物。有關XORTX的更多信息可訪問www.xortx.com。
XORTX是一家藥品公司,其有兩個臨床前進展階段的產品:1)ADPKD的首席,XRx-008計劃; 2)與冠狀病毒/ COVID-19感染有關的急性腎臟和其他急性器官損傷的XRx-101二級計劃。 另外,XRx-225是2型糖尿病腎病的臨床前階段計劃。 XORTX正在努力推進臨床發展階段的產品,以靶向異常的嘌呤代謝和黃嘌呤氧化酶,以降低或抑制尿酸產生。 在XORTX,我們致力於開發藥物以提高患者的生活質量和未來健康。 XORTX的其他信息可在該網站上獲得。
更多信息,請聯繫:
首席執行官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-半導體主任Nick Rigopulos nick@alpineequityadv.com或+1 617 901 0785 |
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