Tolvaptan

Scientists have successfully grown 'mini kidneys' in the lab and grafted them into live mice, revealing new insights into the metabolic defects and a potential therapy for polycystic kidney disease. Scientists at Nanyang Technological University, Singapore (NTU Singapore) have successfully grown 'mini kidneys' in the lab and grafted them into live mice, revealing new insights into the metabolic defects and a potential therapy for polycystic kidney disease. 'Mini kidneys,' or kidney organoids, are kidney-like structures grown in the lab using stem cells. In the study led by NTU's Lee Kong Chian School of Medicine (LKCMedicine), researchers grew the organoids using skin cells derived from patients with polycystic kidney disease (PKD), a prevalent form of genetic condition that affects 1 in 1000 individuals across all ethnicities.* People with PKD often progress to end-stage kidney disease between their 50s and 60s, with the standard treatment options available being dialysis or a kidney transplant. However, dialysis significantly compromises a patient's quality of life, while a transplanted kidney can be challenging to acquire. One other option is the Food and Drug Administration (FDA) approved drug Tolvaptan, which is very costly and has severe side effects on the liver. To address the need for more effective treatment for PKD patients, the NTU research team sought to better understand the disease by engrafting their newly developed mini kidneys into mice. Previous studies were conducted on mini kidneys grown in a dish, which could only partly mimic the kidney structure and function. The NTU scientists engrafted the mini kidneys into live mice to comprehensively replicate the pathological features of kidney disease, including blood flow, fluid movement (tubular fluid) and cellular communication with other organs. Lead investigator Assistant Professor Xia Yun at LKCMedicine said, "Engrafting the kidney organoid in mice provided us with a physiologically sophisticated approach to studying polycystic kidney disease as we were able to successfully emulate critical disease characteristics similar to those observed in human kidney patients." Critical disease characteristics included abnormalities like the spontaneous formation of cysts in the kidneys and the subsequent damage to its tiny tubes. In their study, reported in the scientific journal Cell Stem Cell, the NTU research team said that they believed their engrafted mini kidneys were high quality because cysts sustained without extra stress stimulation or chemicals, even after they were removed from the live mice for further investigations in a dish. In contrast, previous kidney organoids grown in a dish cannot form cysts without stress stimulation. Co-investigator Assistant Professor Foo Jia Nee at LKCMedicine said, "The similarity between the disease manifestation observed in our engrafted mini kidney model and the real-life experiences of polycystic kidney disease patients suggest that growing kidney organoids and engrafting them into live mice could be beneficial in studying the disease and a useful tool to test new treatments." Metabolic defects in polycystic kidney disease Scientists have long known that abnormalities in a structure on kidney cells, or the primary cilium, cause cysts to form in kidneys. However, tests to understand the regulatory mechanism and relationship between the primary cilium and cell metabolism (autophagy) in live mice with PKD, have not been possible until now. By studying the development of PKD in live mice and testing cellular pathways, researchers found evidence that boosting autophagy could reduce the severity of cysts in the mini kidney. After establishing that boosting autophagy could reduce cysts, the NTU scientists shortlisted 22 drugs known for their effects on cell metabolism and tested them in the lab. Results showed that minoxidil, a clinical drug widely used to cure hypertension and hair loss, effectively reduced cyst formation in the novel mouse model. Asst Prof Xia Yun said, "Our study has demonstrated how cysts in polycystic diseased kidneys can be reduced by boosting autophagy, suggesting that this could be a promising treatment for PKD. Moreover, the proven clinical safety of minoxidil may allow it to be quickly re-purposed to treat PKD patients in clinic. However, more research will be needed to establish this potential." Commenting as an independent expert, Associate Professor Ng Kar Hui, Senior Consultant, Division of Paediatric Nephrology, Dialysis and Renal Transplantation, Department of Paediatrics, Khoo Teck Puat -- National University Children's Medical Institute, National University Hospital, said, "Polycystic kidney disease is one of the biggest causes of chronic kidney diseases among adults. An effective treatment may potentially ameliorate the rising numbers of people with kidney failure in Singapore. The establishment of such models in live organisms brings us one step closer to finding more treatment options. In future studies, the NTU team will test the efficacy of minoxidil and adapt the mini kidney models to investigate other burgeoning kidney diseases without a strong genetic underpinning, such as diabetic kidney disease. * Harris, P.C., and Torres, V.E. (2009). Polycystic kidney disease. Annual Review of Medicine. Volume 60, 321-337.

CALGARY, Alberta, March 27, 2024 (GLOBE NEWSWIRE) -- XORTX Therapeutics Inc. ("XORTX" or the “Company”) (NASDAQ: XRTX | TSXV: XRTX | Frankfurt: ANUA WKN: A3UNZ), a biopharmaceutical company focused on developing innovative therapies to treat autosomal dominant polycystic kidney disease (“ADPKD”), is pleased to announce that Dr. Ronald Perrone has joined the Company’s Clinical Advisory Board. Dr. Allen Davidoff stated, “We are excited that Dr. Ron Perrone has agreed to join XORTX’s Clinical Advisory Board. Dr. Perrone brings substantial medical and professional experience as a thought leader, combined with clinical experience treating patients with ADPKD and kidney disease. We are privileged to have Dr. Perrone join our esteemed Clinical Advisory Board alongside current members, Dr. Petter Bjornstad, Dr. Richard Johnson, Dr. Federico Maese, Dr. Anjay Rostogi and Dr. Charles Edelstein. We look forward to the valuable contributions that he can bring to our advanced clinical program and specifically the XRX-OXY-201 registration trial designed to slow progression of ADPKD.” Dr. Ronald Perrone, MD is Professor of Medicine at Tufts University School of Medicine in Boston, Massachusetts. Dr. Perrone is board certified in Nephrology. He did his Internal Medicine residency at Grady Memorial Hospital in Atlanta and Nephrology fellowship at Boston University Medical Center. Ron’s research involves clinical investigations focused on kidney disease with a special emphasis on polycystic kidney disease (“PKD”). He is heavily involved in clinical research in ADPKD clinical trials and works with regulatory agencies such as the US Food and Drug Administration (“FDA”) to contribute to the development of database assessment tools to validate total kidney volume as a biomarker for PKD progression. Dr. Perrone’s focus on translational clinical trial interventions in ADPKD includes trials for Sanofi, Reata, Palladio Biosciences, HALT-PKD, the TAME PKD Metformin trial, TEMPO and REPRISE trials for Tolvaptan. Ron also initiated a PKD Database Consortium in 2007 which led to the creation of the PKD Outcomes Consortium in 2009. The PKD Outcomes Consortium, comprising contributors from academia, the pharmaceutical industry, National Institute of Health (“NIH”), FDA, the Clinical Data Interchange Standards Consortium (“CDISC”), and the Critical Path Institute (C-Path), is creating the groundwork for validation of for biomarkers and clinical trial and regulatory endpoints in ADPKD. This work is ongoing and involves frequent interactions with the FDA and the European Medicines Agency. A full list of Dr. Perrone’s publications can be found at: https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/?term=perrone+rd. 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 www.xortx.com. For more information, please contact: Allen Davidoff, CEO Nick Rigopulos, Director of Communicationsadavidoff@xortx.com or +1 403 455 7727 nick@alpineequityadv.com or +1 617 901 0785 Kim Golodetz, LHA Investor Relations kgolodetz@lhai.com or 1 212 838 3777 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. Forward Looking Statements This press release contains express or implied forward-looking statements pursuant to U.S. Federal securities laws. These forward-looking statements and their implications are based on the current expectations of the management of XORTX only, and are subject to a number of factors and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Except as otherwise required by law, XORTX undertakes no obligation to publicly release any revisions to these forward-looking statements to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. More detailed information about the risks and uncertainties affecting XORTX is contained under the heading “Risk Factors” in XORTX’s Registration Statement on Form F-1 filed with the SEC, which is available on the SEC's website, www.sec.gov (including any documents forming a part thereof or incorporated by reference therein), as well as in our reports, public disclosure documents and other filings with the securities commissions and other regulatory bodies in Canada, which are available on www.sedarplus.ca.