New study to understand cyst growth in autosomal dominant polycystic kidney disease

12 February 2022

With our funding, Dr Joshua Griffiths from the University of Sheffield’s Kidney Genetics Group will try to understand how the stiffness of the skeleton of cells affects cyst growth in patients with autosomal dominant polycystic kidney disease (ADPKD).

The leading cause of kidney failure

ADPKD is a common inherited disease, causing large numbers of fluid-filled cysts to grow in the kidneys. It is a leading cause of kidney failure in the UK and around half of patients will need dialysis or kidney transplant by the age of 60. To date, Tolvaptan is the only drug that has been shown to slow progression of the disease, but many patients are not able to tolerate the side effects and it doesn’t always work well.

Dr Joshua Griffiths

How do gene faults lead to ADPKD?

It is vital that we understand how and why cysts develop so we can design new treatments to prevent or slow the disease and improve quality of life for patients with ADPKD. ADPKD is most often caused by faults in one of two genes, PKD1 or PKD2, which are responsible for making the proteins Polycystin-1 (PC1) and Polycystin-2 (PC2), respectively. However, we don’t know what these proteins do in the body or how problems with them cause ADPKD.

Joshua has identified an interaction between PC1 and another protein called SH3BP1. SH3BP1 is important for controlling the structure of cells, how they move, how they stick to each other, and it also controls a mechanism that brings factors inside the cells, including factors that may cause excessive multiplication of cells. Disrupting any or all of these different roles of SH3BP1 has the potential to cause the cyst development and growth seen in patients with ADPKD.

Over the course of this project, using cells in a dish, Joshua will study the interaction between PC1 and SH3BP1 and whether disruption in this interaction is important for cyst growth and development.

What does this mean for patients?

This could identify a new family of potential drug targets for treatments to slow or stop disease progression in patients with ADPKD.

“I am absolutely delighted to have been offered this award from Kidney Research UK and the Medical Research Council,” said Joshua. “Through this project, I will have a fantastic opportunity to explore why patients with ADPKD develop cysts and significantly improve our understanding of the disease. I believe that this work has the potential to identify new treatments that could improve the lives of patients with ADPKD in the future. This funding will also provide me with the time and support to develop the vital skills needed for me to continue research into kidney disease long into the future.”

Joshua’s work is jointly funded by a Clinical Training Fellowship from Kidney Research UK and Medical Research Council for £271,460.