Tolvaptan

Scientists at Mayo Clinic have uncovered a surprising new way the kidneys conserve water, revealing a hidden backup system that works independently of the hormone long believed to control the process. The discovery emerged when researchers testing an old drug called probenecid expected it to worsen polycystic kidney disease (PKD) but found it actually slowed cyst growth instead.Researchers at Mayo Clinic have discovered a previously unknown way the kidneys help maintain the body's water balance, a finding that could eventually lead to better treatments for polycystic kidney disease (PKD) and other conditions. The study, led by Mayo Clinic nephrologist Fouad Chebib, M.D., was published in the Journal of Clinical Investigation. Scientists have long believed that the body's ability to concentrate urine and avoid dehydration depends mainly on the hormone vasopressin. The new research reveals that the kidneys also have another pathway for regulating water that works independently of vasopressin. "The kidney's ability to regulate water is one of the most fundamental processes in the body," Dr. Chebib says. "It's not every day that you uncover a new way it carries out that function." Hidden Kidney Pathway Discovered The finding expands researchers' understanding of how the kidneys function. By identifying an additional mechanism involved in water conservation, the study adds a new layer to decades of knowledge about kidney physiology. The discovery may be especially important for people with polycystic kidney disease, a genetic disorder that causes fluid-filled cysts to develop in the kidneys. Over time, these cysts can impair kidney function and eventually lead to kidney failure. PKD affects millions of people around the world. In the United States, about 140,000 people have the most common form of the disease, autosomal dominant PKD (ADPKD). Many patients ultimately need dialysis or a kidney transplant. Unexpected Results From a Decades-Old Drug Dr. Chebib's team uses laboratory-grown cell models to study how kidney cysts develop and grow in PKD. During one set of experiments, researchers tested compounds that they expected would worsen the disease by increasing cellular activity linked to cyst growth. One of those compounds was probenecid, a medication originally introduced in the 1940s to help conserve scarce supplies of penicillin by reducing how much of the antibiotic was excreted in urine. "We thought this drug would make the disease process worse," Dr. Chebib says. "Instead, it did the opposite." Rather than accelerating cyst growth, probenecid slowed it down. After repeating the experiments several times and obtaining the same result, the researchers realized they had uncovered something unexpected. How Urate Helps the Kidney Conserve Water The team then investigated why the drug was having this effect. Their research showed that probenecid alters how kidney cells handle urate, a molecule most commonly associated with gout. Inside kidney cells, urate acts as a signaling molecule. It sets off a series of cellular events that move water channels to the cell surface, allowing the kidneys to reabsorb water and concentrate urine. This process can occur without relying on vasopressin, which has traditionally been viewed as the primary regulator of urine concentration. "This represents a distinct pathway from what is described in traditional physiology models," Dr. Chebib says. "It demonstrates that the kidney has an additional mechanism to preserve water." Potential Benefits for PKD Treatment The discovery could help address one of the major drawbacks of current PKD treatment. The only approved medication for slowing PKD progression is tolvaptan. The drug works by blocking vasopressin, which helps reduce cyst growth. However, it also causes patients to produce very large amounts of urine, often 6 to 7 liters per day. For many people, that side effect can be difficult to manage and may lead them to discontinue treatment. In preclinical studies and a small clinical trial, researchers found that adding probenecid reduced both urine volume and nighttime urination while maintaining the effectiveness of treatment. On average, patients experienced about a 30% reduction in urine volume after taking probenecid. Many went from waking up multiple times each night to urinate to waking only about once per night. Participants also reported improvements in their quality of life. "The goal is to preserve the therapeutic benefit of tolvaptan while reducing its burden," Dr. Chebib says. Looking Beyond Probenecid Although the results are encouraging, the researchers do not see probenecid itself as a long-term answer. The medication is several decades old, affects multiple biological systems, and is not widely available today. Instead, the team hopes to use what they learned from the drug to create new therapies that specifically target the newly identified pathway. "Probenecid helped us uncover the mechanism," Dr. Chebib says. "Our goal is to take this insight and develop therapies designed specifically for this pathway." A Personal Motivation For Dr. Chebib, the research is connected to a deeply personal experience. His interest in kidney disease began after his father was diagnosed with PKD. "This has been a long and deeply purposeful journey," he says. "It started with a personal motivation and led to something that could ultimately benefit patients."

San Francisco-based SonoThera has closed an oversubscribed USD 125 million Series B financing round to advance its ultrasound-mediated nonviral genetic medicine platform into clinical development, with lead programs targeting Duchenne muscular dystrophy and autosomal dominant polycystic kidney disease. The funding round signals substantial investor conviction in a delivery approach that diverges from viral vector-based gene therapies, positioning the company to initiate its first clinical trial in DMD in 2027. Vida Ventures led the round, with new participants ARK Invest, CureDuchenne Ventures, Leaps by Bayer, Otsuka Pharmaceutical, SymBiosis, UCB Ventures SA, and Vivo Capital. Existing investors ARCH Venture Partners, Alexandria Venture Investments, Duquesne Family Office, Illumina Ventures, Johnson & Johnson Innovation — JJDC, Inc., Medical Excellence Capital, RA Capital, and Vertex Ventures HC also participated. In connection with the financing, Rajul Jain, M.D., Managing Director at Vida Ventures, and Rakhshita Dhar, M.S., Vice President and Head of Healthcare Venture Investments at Leaps by Bayer, have joined SonoThera’s board of directors. The company said proceeds will advance its DMD and ADPKD genetic medicine programs into clinical trials, expand its pipeline across multiple organ systems, and further scale its proprietary platform technologies. No prior funding rounds were disclosed in the announcement, making this the first publicly confirmed capital raise for the company. The platform science: RIPPLE and PORE SonoThera’s approach integrates two proprietary technologies. The RIPPLE ultrasound delivery system uses widely available, US FDA-cleared diagnostic ultrasound equipment combined with commercially approved ultrasound contrast agents to create a noninvasive, outpatient procedure estimated to take approximately one hour or less. When applied to target tissues, the ultrasound energy transiently increases cell membrane permeability, enabling uptake of genetic payloads that would not otherwise cross cellular barriers efficiently. The PORE payload engineering platform supports a range of genetic medicine modalities, including DNA and RNA therapeutics, gene editing, and gene silencing approaches. Together, the two systems are designed to enable targeted, redosable delivery of large genetic payloads — a combination of attributes that has proved difficult to achieve with viral vectors. Conventional adeno-associated virus gene therapies face well-documented constraints: packaging capacity is limited to approximately 4.7 kilobases, pre-existing immunity can blunt efficacy, immune responses to the viral capsid can pose safety risks, and redosing is generally not feasible. SonoThera’s nonviral platform is designed to address each of these limitations, and the company has reported preclinical delivery of full-length dystrophin — the gene mutated in DMD, which at approximately 14 kilobases far exceeds AAV capacity — as well as RNA-based payloads for gene silencing. Targeted delivery and expression have been demonstrated across skeletal muscle, heart, liver, kidney, adipose tissue, and brain in preclinical studies. The lead program targets Duchenne muscular dystrophy, a severe progressive muscle-wasting disease caused by mutations in the dystrophin gene. Current approved therapies include exon-skipping approaches that restore partial dystrophin function, but delivery of a full-length dystrophin construct has remained an unresolved challenge for the field. SonoThera has stated its intention to initiate a first-in-human DMD trial in 2027. The second lead program addresses autosomal dominant polycystic kidney disease, a common inherited kidney disorder driven by mutations in the PKD1 or PKD2 genes. Current standard of care includes tolvaptan, which slows cyst growth but does not address the underlying genetic defect. An ADPKD genetic medicine that could silence or correct the causative mutation in kidney tissue would represent a distinct therapeutic approach. The participation of CureDuchenne Ventures and UCB Ventures SA as new investors is strategically notable. CureDuchenne is a patient advocacy organization with a dedicated venture arm focused on DMD programs including a recent investment in Tevard Biosciences, and UCB has established commercial interests in rare neurological and muscular diseases. The nonviral delivery landscape for genetic medicines is competitive, with lipid nanoparticles representing the dominant alternative to viral vectors. LNP-based approaches have achieved regulatory approval in liver-targeted applications — including RNA interference therapies and mRNA vaccines — but extrahepatic delivery remains technically challenging. SonoThera’s ultrasound-guided approach offers tissue specificity through physical targeting rather than relying solely on ligand-receptor interactions or passive organ accumulation, which the company argues enables access to muscle, kidney, and other non-hepatic tissues that LNP platforms have struggled to reach reliably. This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/ Your email address will not be published. Required fields are marked * Comment * Name * Email * Website Copyright © 2026. AllSci Corp. All rights reserved.