The US-based Dent Disease Foundation has awarded the Oliver Wrong Research Award to a project led by Dr Gerard Cantero-Recasens, principal investigator of the Kidney Pathophysiology group at the Vall d’Hebron Research Institute (VHIR). The award, worth $50,000, will enable the development of a kidney organoid-based platform to study Dent disease type 1 (DD1) and identify drugs that could slow its progression.

DD1 is a rare disease that affects the kidneys and is caused by mutations in the CLCN5 gene. These mutations disrupt the functioning of the proximal tubule, a part of the kidney responsible for reabsorbing substances that are filtered into the urine. Over time, these changes can lead to fibrosis and kidney failure. Approximately 50% of patients require dialysis in adulthood, and there are currently no specific treatments or biomarkers available to predict how the disease will progress.

Over the past decade, progress has been made in understanding the mechanisms that cause DD1. However, the models commonly used to study the disease do not adequately reproduce human physiology. The new project aims to overcome this limitation by using kidney organoids, three-dimensional models that reproduce some of the characteristics and functions of kidney tissue. These “mini-kidneys” reproduce the structure of the proximal tubule more faithfully than traditional cell cultures. This is particularly relevant for such a complex organ as the kidney, which is made up of more than 51 different cell types, whose interactions are important for its functioning.

A platform to identify new therapeutic options

In the first phase of the study, the team will establish organoids derived from mouse models* of DD1. Twenty drugs that are already commercially available and could be useful in treating the disease will be tested in these models. Candidate drugs will be selected with the support of artificial intelligence and mathematical models, taking into account the biological mechanisms they target and their role in kidney function.

In parallel, human kidney organoids will be generated from cells obtained from three patients with DD1 who have different patterns of clinical progression. This will allow the project to study the disease in different contexts and reproduce some of the variability found among patients, offering an advantage over animal models.

In the second phase, the drug candidates that have shown the most promising results in the mouse models will be validated in the human organoids.

“The aim is to establish a platform that will make it possible to study the disease and assess potential treatments more accurately. In this way, we hope to reduce the time needed to translate preclinical findings into future clinical trials,” explains Dr. Gerard Cantero-Recasens, principal investigator of the Kidney Pathophysiology group at VHIR.

A collaborative project with potential applications in other kidney diseases

The study will involve close collaboration with the Paediatric Nephrology Department at Vall d’Hebron University Hospital, led by Dr Gema Ariceta. This collaboration will strengthen the link between research and patient care. “The platform developed through this project could open up new avenues for studying other kidney diseases and help identify treatments for patients who currently have few therapeutic options,” says Dr. Gema Ariceta, head of the Paediatric Nephrology Department at Vall d’Hebron University Hospital and of Kidney Pathophysiology group at VHIR.

The project will also be carried out in collaboration with the University of Edinburgh, where Dr Gerard Cantero-Recasens completed a research placement to gain experience in generating kidney organoids.

Support from the Dent Disease Foundation

The Dent Disease Foundation is a US-based non-profit organisation dedicated to raising awareness of Dent disease, connecting patients and families, and promoting medical research. Through the Oliver Wrong Research Award, the foundation supports projects that contribute to the development of new diagnostic and treatment methods for Dent disease types 1 and 2.

In the case of the project led by Dr. Gerard Cantero-Recasens, the award particularly recognised the team’s track record in Dent disease research, the potential of the findings to benefit patients, and the project’s ability to help identify new treatments.

*Institutional statement on the use of animals in research