Recipient organisationNIHR Newcastle Biomedical Research Centre
NIHR supportRecorded as supported by this research centre
PeriodMar 2025 — Feb 2026
In plain English
AI plain-English summary
A drug that forces cells to skip over faulty genetic instructions could slow kidney failure in people with the most common inherited kidney disease. Around 10% of patients worldwide who need dialysis or a kidney transplant have autosomal dominant polycystic kidney disease (ADPKD), caused by a single mutated gene. In roughly 78% of cases, the mutation is a “nonsense” change in the PKD1 gene—a premature stop signal that truncates a crucial protein, leading to fluid-filled cysts that destroy kidney tissue. Existing treatments are limited. This project tests whether a novel compound can make cells “read through” that stop signal, restoring enough functional protein to slow cyst growth. The researchers will grow kidney cells shed naturally into patients’ urine, preserving each person’s unique genetic and cellular features. They will measure how well the compound corrects defects in the cells’ primary cilia—tiny antenna-like structures that sense fluid flow and are disrupted in ADPKD. If the compound works in these patient-derived cells, the data will support a clinical trial and establish urine-derived cells as a non-invasive biomarker for treatment success.
View original technical description
We propose using deep phenotyping of autosomal dominant polycystic kidney disease patient urine-derived renal epithelial cells (URECs) to evaluate the effectiveness of nonsense read-through treatments. Specifically, we will characterize the primary ciliary phenotype in URECs with nonsense mutations in PKD1 and assess their response to a novel nonsense read-through compound. This study will provide proof of concept and preclinical data to support a clinical trial, establishing URECs as a potential biomarker of therapeutic success for nonsense read-through compound treatment. Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of kidney failure and accounts for ~10% of all patients globally needing dialysis or a kidney transplant (Mader, Mladsi et al. 2022). It is the fourth most common cause of kidney failure. The molecular genetics of ADPKD are well described with PKD1 variants contributing to around 78% of cases and PKD2 alleles contributing to 15% of cases. In North East England we have a well described cohort of ADPKD patients (Gkekas, Tang et al. 2022) that are documented within our Clinical Vison database and are recruited to the national Renal Rare Diseases database (RaDaR). The top research priority of the PKD Charity is “What treatments can be developed that slow or prevent progression of ADPKD and improve patients’ quality of life?“ We are driven by a desire to meet this need. The concept of using urine-derived renal epithelial cells (URECs) involves isolating epithelial cells shed into the urine and culturing them in vitro to study kidney-related diseases. URECs offer a non-invasive way to obtain patient-specific cells, preserving genetic and phenotypic characteristics relevant to kidney function and pathology. In the context of disease modeling, such as in ADPKD, URECs provide a platform to investigate cellular mechanisms, test therapeutic responses, and develop biomarkers for monitoring treatment efficacy.
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