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New drug compound could tackle major life-limiting kidney disease ADPKD by Rosie Loft

21 June 2019

Scientists from the University of Sheffield and the USA are developing a new class of drugs to treat autosomal dominant polycystic kidney disease (ADPKD), which is a major cause of kidney failure. Over the last 12 years the Sheffield team have received around £700,000 from Kidney Research UK, which has helped them to develop the skills and knowledge to contribute to this exciting project.

Working with Glasgow-based biotech company Mironid and colleagues in the US, the Sheffield researchers have tested a compound developed by Mironid in the lab to treat ADPKD, an hereditary disease which affects over 60,000 people in the UK and around 12 million people worldwide. The findings have been published in the prestigious US journal Proceedings of the National Academy of Sciences (PNAS).

Charity funding

Kidney Research UK has funded work on ADPKD at the University of Sheffield for several years, helping to develop vital knowledge about how the disease develops and how it might be managed.

Chief executive of the charity, Sandra Currie, said: “We are proud to have supported several ADPKD studies led by Professor Ong and his team at Sheffield over the years. Most recently, we funded Professor Ong’s investigations into how to control the ‘messenger molecule’, cyclic AMP, which affects how quickly cysts grow and expand in the kidneys. It is really encouraging news that this collaboration with Mironid has now tested a compound which reduces levels of the cyclic AMP molecule in the lab. This could bring new hope to the 12 million people living with ADPKD worldwide – we look forward to further developments.”

Stopping cysts growing

ADPKD is caused by a genetic fault that stops kidney cells developing normally and causes cysts to form inside the kidneys. The cysts, which are like fluid-filled blisters, grow and eventually destroy normal kidney tissueand the kidneys stop working properly.


This leaves patients needing life-saving treatments, such as dialysis or a kidney transplant.

In ADPKD cells, cysts develop and grow because they produce higher than normal levels of a ‘messenger molecule’ called cyclic AMP (or cAMP). One of the many known functions of cAMP is to tell cells when to divide and when to release fluid.

The new compound discovered by Mironid activates an enzyme called PDE4, whose natural role is to break down cAMP. Using cell and tissues from ADPKD patient kidneys, researchers at Sheffield and the US have found that that when the Mironid compound switches PDE4 on, levels of cAMP in the disease cells fall and the number and fewer cysts grow.

Personalised treatment potential

The reversible nature of the compound means it could rapidly and accurately control PDE4 activity in patients, according to the dose given. This suggests that a future treatment for ADPKD could be tailored to an individual patients’ needs and the severity of their disease. In theory, the compound could also stop cyst forming due to ADPKD in other organs, especially in the liver.

Kidney Research UK funded Professor Albert Ong, a consultant nephrologist and professor of renal medicine who led the Sheffield work, said: “As a researcher, it’s very exciting to be involved in the early stage development of a completely new class of drugs.

"Like most genetic diseases, ADPKD cannot be cured. This discovery gives me hope for the many patients I see in my clinics that there could be another effective new treatment in the future to keep the disease in check for much longer, either on its own or in combination with other drugs such as tolvaptan.

“I would love to think that ADPKD could one day be a disease that people can successfully manage throughout their natural lives, rather than one that could shorten their lives.”

Mironid's next step is to refine the compounds and develop a new medicine to treat ADPKD patients, which will then be tested in a clinical trial.

View the full paper and find out more about polycystic kidney disease.

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