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 announce a presentation by Dr. Allen Davidoff at the Rare and Genetic Kidney Disease Summit, in Boston, Massachusetts at 10:30 am ET, Thursday December 12, 2024. The presentation entitled “Autosomal Dominant Polycystic Kidney Disease – Genetic and Environmental Factors → Evidence for Aberrant Purine Metabolism as a Second Hit Determining Disease Progression.”
The presentation highlights XORTX recent pioneering discoveries in the field of Autosomal Dominant Polycystic Kidney Disease (“ADPKD”), and recent peer-reviewed, independent, published research reports identifying genetic factors that influence over-expression of xanthine oxidase (“XO”) and play a role in several diseases, including kidney disease.
These ground-breaking findings suggest that genetic factors that influence aberrant purine metabolism may influence the rate of progression of ADPKD.
Dr. Allen Davidoff, CEO of XORTX, stated, “The recent identification of genetic factors that increase the expression of XO, and/or contribute to chronic hyperuricemia support the concept of a “second hit” – a factor or factors that accelerate the rate of disease progression when present. These new discoveries are an important first step in our understanding of why ADPKD progression may vary substantially even amongst family members. These discoveries highlight an opportunity to develop a personalized therapeutic approach for individuals whose unique genetic factors predisposed them to ADPKD, and the need for XO 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 provide an opportunity to further understand the role of these newly identified genetic factors in individuals with progressive kidney disease.”
About Xanthine Oxidase
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, polycystic kidney disease1,5 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.
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 health of kidney disease patients. Additional information on XORTX is available at www.xortx.com
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