Faculty of Biological Sciences

Research Bulletin

Findings provide new therapeutic route for rare kidney disease

15th June 2010

Recent findings provide a new focus for future therapies for Dent's disease, for which there is currently no cure.

Scientists from the University of Leeds have discovered the mechanisms of a protein known to play an active part in the inherited kidney disorder, Dent's disease. The findings provide a new focus for future therapies for the disease, for which there is currently no cure. Dent's disease is an extremely rare illness caused by a genetic mutation on the X chromosome. Affecting mostly men, its main symptom is kidney stones often followed by a deterioration of kidney function and in many cases chronic kidney failure. Treatment for the disease is focused on alleviating symptoms and can involve kidney transplant. Scientists from the University's Faculty of Biological Sciences have uncovered the role of a transporter protein, called CLC-5, which is known to be faulty in many sufferers of Dent's disease. Lead researcher Dr Jonathan Lippiat says, "This is a rare genetic disease so it's impossible to know the exact number of sufferers worldwide. Dent's disease could be the underlying cause of kidney stones or kidney failure for a larger number of people and it could be that a number of Dent's sufferers go undiagnosed. The faulty gene itself has been known about for quite a while, but there's been no concrete evidence about the function it fulfils. That's why we're excited by these findings - they provide us with a whole new area to examine in the search for therapies for Dent's disease." In a research project supported by the Wellcome Trust, Dr Lippiat and his team have discovered that CLC-5 facilitates a crucial function by allowing certain ions to pass through cell membranes so they can reach the places they are needed. The kidneys filter our blood, removing waste, but minerals and hormones that we need to remain healthy need to be reabsorbed. In order for the cells in the kidney to reabsorb effectively, a process called endocytosis takes place to allow larger molecules to travel through the cell membrane. In endocytosis, a compartment is created in the cell membrane for the molecule to enter. This compartment - or endosome - needs to be acidic in order for the process to work effectively. The research findings show that CLC-5 delivers protons into endosomes, which causes acidification to occur, so when it CLC-5 is faulty, endocytosis cannot take place effectively. "If endocytosis can't take place we lose vital vitamins and hormones," says Dr Lippiat. "CLC-5 is actually part of a family of proteins, some of which are implicated in other diseases, so these findings could have important consequences when we're looking at the role of other proteins in the same family."

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Chris Hassall, Royal Society (Dec 2014), £14,500

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Darren Tomlinson and colleagues in Experimental Oncology, YCR (Oct 2014), £69,480

Andrew Macdonald, Jamel Mankouri, Kidney Research Fund UK (Oct 2014), £58,878

Mike McPherson and colleagues in Dentistry and Engineering, Wellcome Trust (Oct 2014), £58,437

Dave Westhead and colleagues in Experimental Haemotology, Leukaemia & Lymphoma Research (Sep 2014), £281,424

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Michelle Peckham, Mark Harris, Rao Sivaprasadarao, Eileen Ingham, Nic Stonehouse, Nikita Gamper, Wellcome Trust (Sep 2014), £192,763

Neil Ranson, BBSRC (Aug 2014), £355,253

Stuart Egginton, BHF (Aug 2014), £271,094

Darren Tomlinson, Mike McPherson, Technology Strategy Board (Aug 2014), £98,665

Peter Henderson, Leverhulme Trust (Aug 2014), £15,222

Mike McPherson (and colleagues in the School of Chemistry), EPSRC (Jul 2014), £819,880

Peter Stockley, Neil Ranson, BBSRC (Jul 2014), £455,787

Sheena Radford, Univesity of Michigan (Jul 2014), £138,452

Ryan Seipke, British Society Antimicrobial Chemistry (Jun 2014), £11,960

John Trinick, BHF (Jun 2014), £222,614

Chris West, Leverhulme Trust (Jun 2014), £181,241

Jon Lippiat, Darren Tomlinson, BBSRC (May 2014), £125,174

Christine Foyer, Royal Society (May 2014), £24,000

David Brockwell, Sheena Radford, Medimmune Ltd (Apr 2014), £337,661

Peter Stockley, Wellcome Trust (Apr 2014), £251,019

Mike McPherson, Wellcome Trust (Apr 2014), £146,596

Andrew Macdonald, Kidney Research Fund UK (Apr 2014), £127,237

Elwyn Isaac, DEFRA (Apr 2014), £126,512

Mike McPherson (and colleagues in School of Design), Technology Strategy Board (Apr 2014), £114,350

Paul Millner, Peter Stockley, Darren Tomlinson, YCR (Apr 2014), £95,874

Carrie Ferguson, Karen Birch, Shaunna Burke, Heart Research UK (Apr 2014), £60,140

Tim Benton, Technology Strategy Board (Apr 2014), £24,969

Bill Kunin, Technology Strategy Board (Apr 2014), £21,244

Dave Westhead, MRC (Apr 2014), £18,304

Brendan Davies, BBSRC (Mar 2014), £451,829

Jim Deuchars, MRC (Mar 2014), £300,000

Urwin, Howard Atkinson, British Potato Council (Mar 2014), £69,953

Adam Kupinski, Children with Cancer (Mar 2014), £50,000

Anastasia Zhuravleva, Royal Society (Mar 2014), £14,973

Urwin, Howard Atkinson, Agriculture & Horticulture Develpmnt Brd (Mar 2014), £13,990

Alison Baker, Steve Baldwin, BBSRC (Feb 2014), £403,439

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Brendan Davies, BBSRC/Bayer Crop Science SA-NV (Jan 2014), £470,053

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Elwyn Isaac, EU (Jan 2014), £179,445

Dave Westhead, Leukaemia & Lymphoma Research (Jan 2014), £105,937

Eileen Ingham, Joanne Tipper, Depuy International Ltd (Jan 2014), £48,121

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