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."


Recent Grants

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

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

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

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

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

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

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

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

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

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

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

Sarah Zylinski, BBSRC (Feb 2014), £355,869

Dave Lewis, Nigel Hooper, Tony Turner, Hugh Pearson, James Duce, Alzheimer's Society (Feb 2014), £29,871

Ronaldo Ichyama, Samit Chakrabarty, International Spinal Research Trust (Jan 2014), £304,600

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

Adrian Goldman, Steve Baldwin, Stephen Muench, Thomas Edwards, Arwen Pearson , BBSRC (Jan 2014), £467,103

Stefan Kepinski, BBSRC (Jan 2014), £359,269

Elwyn Isaac, EU (Jan 2014), £179,445

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

John Barr, Thomas Edwards, MRC (Dec 2013), £469,505

Alex O'Neill, MRC (Dec 2013), £349,017

Darren Tomlinson, Yorkshire Cancer Research (Nov 2013), £142,334

Nikita Gamper, MRC (Nov 2013), £336,563

Keith Hamer, Alison Dunn, NERC (Nov 2013), £47,233

Alan Berry, Wellcome Trust (Oct 2013), £749,365

Urwin, Howard Atkinson, BBSRC (Oct 2013), £360,508

Eileen Ingham, Stacey-Paul Wilshaw, NHS R&D (Oct 2013), £356,623

Sheena Radford, BBSRC (Oct 2013), £329,906

Nigel Hooper, Alzheimer's Research (Oct 2013), £327,075

Eileen Ingham, EPSRC (Oct 2013), £276,751

David Beech, BHF (Oct 2013), £109,974

Mark Harris, Medical Research Foundation (Oct 2013), £34,455

James Dachtler, Royal Society (Oct 2013), £15,000

Ade Whitehouse, Teresa Rosenbaum Golden Charitable Trust (Oct 2013), £10,000

Jurgen Denecke, BBSRC (Sep 2013), £382,093

Andy Cuming, EU (Sep 2013), £257,714

Paul Knox, BBSRC (Sep 2013), £411,948

Vas Ponnambalam, Leverhulme Trust (Sep 2013), £245,031

Peter Meyer, EU (Sep 2013), £242,166

Dave Rowlands, Nic Stonehouse, EU (Sep 2013), £202,556

Derek Steele, BHF (Sep 2013), £103,629

Joan Boyes, NC3Rs (Sep 2013), £90,000

Peter Stockley, Royal Society (Sep 2013), £11,400

Darren Tomlinson, Leverhulme Trust (Sep 2013), £5,645

Nic Stonehouse, Dave Rowlands, BBSRC (Aug 2013), £574,906

Eileen Ingham, Wellcome Trust (Aug 2013), £191,470

Adrian Goldman, Royal Society (Aug 2013), £75,000

Mike McPherson, Wellcome Trust (Aug 2013), £40,000

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