ADPKD News Summary

Mayo Clinic researchers published in the Journal of Clinical Investigation a previously unknown kidney pathway: urate regulates urine concentration independently of vasopressin. This challenges decades of established physiological understanding.

Led by Dr. Fouad Chebib, the study shows that urate — traditionally associated with gout — plays a critical role in kidney water conservation. For ADPKD, this is significant: the only approved drug (tolvaptan) targets the vasopressin V2 receptor, and the urate pathway offers an entirely new therapeutic target.

Source: Journal of Clinical Investigation / CancerIlles (2026-09-11) · View article

Nature Scientific Reports published a study showing that mebendazole, an anthelmintic drug, slows cyst progression and improves renal function in a Pkd1 ADPKD mouse model by disrupting microtubule polymerization.

The study found that microtubule dynamics are enhanced in Pkd1-deficient cells via GSK3β activation. This is the first identification of dysregulated microtubule dynamics as a previously unrecognized mechanism in ADPKD pathogenesis, suggesting mebendazole as a potential drug-repurposing strategy.

Source: Nature Scientific Reports (2026-09-11) · View article · DOI

PYC Therapeutics announced that the first patient has been dosed in the open-label extension study for PYC-003. The extension study provides longer-duration safety and tolerability data, with patients continuing to receive PYC-003 per the original protocols.

PYC-003 is an RNA drug targeting the miR-17 binding site on PKD1 mRNA with a cell-penetrating peptide. 12-month total kidney volume (TKV) data from the Phase 1a/1b program is expected in late 2027, with registrational study data to follow.

Source: Kalkine Media (2026-09-11) · View article

On PKD Awareness Day (Sept 4), the PKD Foundation called for public support of the PKD Cures Act (H.R. 9169) — the first federal legislation in U.S. history devoted exclusively to PKD research. Introduced in June 2026 by bipartisan House members, the bill would expand NIH research, speed clinical trials, and establish a long-term federal research roadmap.

Walk for PKD fundraising events run nationwide through September and October. Since 2000, the walks have raised over $36 million for PKD research. Approximately 500,000 people in the U.S. live with PKD.

Source: PRNewswire / PKD Foundation (2026-09-04) · View article · PKD Cures Act details

CDISC, in partnership with the PKD Foundation and Critical Path Institute, released TAUG-PKD Version 2.0, helping researchers worldwide generate more comparable, reusable, and regulatory-ready data to accelerate discovery for both ADPKD and, for the first time, ARPKD.

Version 1.0 incorporated data from CRISP and HALT-PKD trials and supported the regulatory qualification of total kidney volume (TKV) as a disease progression biomarker for ADPKD.

Source: PKD Foundation (2026-09-04) · View article

A bioRxiv preprint demonstrates that collecting duct-targeted lipid nanoparticles (LNPs) delivering Pkd2 mRNA reversed established cystic disease in Pkd2-deficient mice, restoring renal architecture and reducing fibrosis and inflammation.

A single dose also reduced cyst burden and improved renal function in a Pkd1-deficient model, suggesting the strategy may work across genetic backgrounds. This is the first study showing mRNA replacement therapy directly restoring polycystin expression and reversing formed cysts.

Source: bioRxiv preprint (2026-06-05) · View article

Frontiers in Medicine published a Chinese single-center prospective open-label trial: 89 rapid-progression ADPKD patients on tolvaptan for 2 years showed left kidney TKV mean change of -70.2 mL (6 months) and -47.8 mL (12 months), with stable eGFR and no major hepatic/renal toxicity.

80% had family history, 40% had polycystic liver disease, 65.6% had hypertension. Most common daily doses: 60mg (31.1%) and 45mg (26.7%). This provides local Chinese evidence supporting tolvaptan efficacy and safety.

Source: Frontiers in Medicine (2026-03-12) · View article · DOI

Under China's "pilot access" policy, Shanghai Jiao Tong University Affiliated Ruijin Hospital Hainan (Boao Lecheng Pilot Zone) has officially introduced tolvaptan for ADPKD, issuing the first domestic prescription.

The first patient is a 53-year-old man from Zhejiang, diagnosed with ADPKD for over 20 years. He started tolvaptan in February 2026 under Dr. Xie Jingyuan's team, titrated to 45mg AM / 15mg PM by July. The drug is not yet commercially available in China — it is approved only within the Lecheng Pilot Zone. Indication: ADPKD with CKD showing signs of rapid progression, to delay cyst and kidney function decline.

The model uses dual-hospital coordination: comprehensive evaluation at Ruijin Shanghai, medication at Ruijin Hainan, with ongoing monitoring of kidney function and electrolytes.

Source: Sina Finance / CCTV Media (2026-09-09) · Sina Finance · CCTV Media

PYC Therapeutics presented PYC-003 Phase 1 safety data at the ANZSN annual meeting. PYC-003 is an RNA drug targeting the miR-17 binding site on PKD1 mRNA, with a cell-penetrating peptide to enhance kidney cell uptake.

All single ascending dose cohorts (healthy volunteers + ADPKD patients) showed zero treatment-related serious adverse events. No changes in serum electrolytes, creatinine, liver function, or renal injury biomarkers (KIM-1, NGAL).

Next: Phase 1a SAD data expected H2 2026, Phase 1b MAD and open-label extension data expected CY 2027. ADPKD affects ~12.5 million people globally, with ~95% currently without treatment options.

Source: StockwireX (2026-08-31) · View article

A Yale team published a study in the Journal of Clinical Investigation identifying upstream open reading frames (uORFs) in the PKD1 gene that limit polycystin-1 (PC1) translation efficiency.

In genetically engineered mouse models, disrupting these uORFs increased PC1 levels 2-4 fold. This supports the therapeutic strategy of "boosting polycystin production" rather than "fixing the mutant gene," consistent with current anti-miR-17 oligonucleotide and pharmacochaperone approaches.

Source: Medical Xpress (2026-08-25) · View article · JCI paper

The PKD Foundation published a comprehensive review of the current ADPKD therapeutic pipeline across four directions:

1. Gene-directed therapies: Farabursen (Novartis, anti-miR-17, Phase 3 initiation being scheduled), PYC-003 (PYC Therapeutics), VX-407 (Vertex pharmacochaperone, Phase 2a AGLOW trial ongoing).

2. Metabolic pathways: SGLT2 inhibitors (dapagliflozin + tolvaptan combination showed additive benefit), empagliflozin EMPA-PKD trial, GLP-1 receptor agonists.

3. Paracrine signaling: PAPP-A inhibitors significantly reduced cyst growth and preserved kidney function across three preclinical mouse models.

4. Gene editing/gene therapy: Single-treatment curative therapies becoming a realistic possibility.

The review emphasizes two key conceptual shifts: ADPKD is "dosage-dependent" not "on or off" — even partial restoration of polycystin levels may be therapeutic; and early cystic changes may be reversible.

Source: Life Science Daily (2026-08-18) · View article

South Korea's Mezzion Pharma announced expanding Udenafil (a PDE5 inhibitor originally developed for Fontan patients) into ADPKD, proceeding directly to Phase 2b trials in Korea and the US.

Animal model results from Mayo Clinic collaboration showed: 50-60% cyst reduction, significant BUN improvement (P<0.001), and improvement in cardiac hypertrophy indicators. Efficacy was verified stepwise from cells to kidney tissue to live animal models.

Source: EDAILY (2026-08-08) · View article

SCYNEXIS initiated a Phase 1 study of SCY-770, a first-in-class oral direct AMPK activator. Preclinical data demonstrated inhibition of cyst cell proliferation and reduction of cyst growth in the kidney.

The drug has a well-characterized safety profile in over 270 clinical trial participants. Phase 1 dose-optimization data expected Q3 2026, with Phase 2 proof-of-concept initiation planned for Q4 2026.

Source: SCYNEXIS press release (2026-06-30) · View article

The ANCHOR study (Phase 2) by AbbVie and Calico Life Sciences is enrolling. The trial spans 231 sites across 9 countries, planning to enroll 240 adult ADPKD patients.

Dosing: intravenous ABBV-CLS-628 or placebo every 4 weeks for 92 weeks. Primary endpoint: rate of change in total kidney volume (TKV) at Week 96. Secondary endpoints include eGFR change.

Source: ClinicalTrials.gov (updated 2026-09-01) · View article

An open-label randomized controlled crossover trial (27 ADPKD patients) evaluated the additive effect of the SGLT2 inhibitor dapagliflozin in patients already on tolvaptan.

Results: Adding dapagliflozin significantly attenuated the eGFR (cystatin C) decline slope (P=0.003) and 6-month TKV change (-0.44% vs +5.04%, P=0.01). This suggests SGLT2 inhibitors may provide additional benefit on top of tolvaptan.

Source: Kidney International Reports (2025) · View article