Research looking at repurposing drugs to treat polycystic kidney disease shows promising new results

31 July 2025

In new results, published in Communications Medicine, Professor Colin A Johnson and researchers at the University of Leeds and University of Sheffield, with support from Kidney Research UK and the PKD Charity, have identified disease pathways in polycystic kidney disease (PKD) and shown that they can be targeted with existing drugs, aiming to get new treatments to patients faster.

The need for new PKD treatments

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent form of polycystic kidney disease (PKD) and the most common inherited condition to affect the kidneys. ADPKD is a major cause of kidney failure, affecting 70,000 people in the UK and up to 12 million people worldwide.

Currently, Tolvaptan is the only treatment available for ADPKD. Although Tolvaptan slows the decline of kidney function, it is not a cure and many patients report side effects, so new treatments are urgently needed.

What are cilia and why are they important?

Cilia are tiny, antennae-like structures on the surface of cells that act as sensors. The cell uses the information from cilia to change and adapt to its surroundings. Several different diseases, including PKD, are linked to inherited problems in cilia formation known as ciliopathies. In PKD, incorrectly formed cilia lead to fluid-filled cysts gradually replacing healthy kidney tissue, resulting in eventual kidney failure.

Testing existing drugs and their targets to uncover new treatments

In this study, Colin and the team tested a range of drugs that are already in development to see what impact they would have on laboratory models of cilia-based disease. They also looked carefully at the targets of any successful drugs within the cilia to better understand how the drugs worked.

The results showed that a protein called ROCK2 plays an important role in cilia formation and highlighted that drugs currently being used to block ROCK2 could offer an important treatment approach for PKD.

When tested on kidney organoids (miniature lab grown models of kidneys), initial results suggested that drugs which specifically target ROCK2 could be a potential treatment option for PKD.

Colin added “Our results suggest that blocking ROCK2 could offer a new and effective approach to treating the cause of PKD. Although further investigation is needed, by focusing on drugs that are already in use, we hope to speed up the time it takes for new medications to reach patients."

Image is split into 4 squares. Each square shows staining which is blue and pink.

Top: stained models of kidney organoids where the arrows indicate cysts. Bottom: stained sections of kidney organoids.

Male sat on a brown leather sofa, draping his hands over the side. He is wearing a pale blue shirt and brown suit style jacket.

Professor Colin A Johnson

Translating the research findings into patient benefit

Following the promising results seen in this study, Colin and the team are keen to carry out additional experiments in pre-clinical models to gather as much data as possible before progressing the treatments to clinical studies.

“Thanks to support by Kidney Research UK, we have been able to further our drug repurposing work to include organoid models and have seen promising results. Our results suggest that inhibiting ROCK2 could offer an important new treatment approach for diseases that are caused by defects in the cilia, including polycystic kidney disease.

Working in partnership with our colleagues at the University of Sheffield, we will now build further evidence to allow us to move into clinical trials.” Colin A Johnson.

New treatments urgently needed

Elaine Davies, Director of research operations commented: “We recognise that new treatments are urgently needed for patients and generations of families that are affected by polycystic kidney disease; these results from Colin and his colleagues present us with a new approach and new hope.

Their work provides us with more knowledge about the pathway that underpins cilia-related disease and highlights the benefits of studying drugs already in development in order to speed up the search for effective new treatments for PKD.”