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

Alan Berry, Wellcome Trust (Oct 2015), £752,365

Urwin, Howard Atkinson, BBSRC (Oct 2015), £200,293

Eric Hewitt, Andrew Macdonald, Yorkshire Kidney Research Fund (Oct 2015), £46,621

Ade Whitehouse, Alison Ashcroft, Ian Carr, BBSRC (Sep 2015), £438,975

Dave Westhead, Leukaemia & Lymphoma Research Leukaemia & Lymphoma Research (Sep 2015), £430,567

Shaunna Burke, Andrea Utley, Sarah Astill, Arts Council of England (Sep 2015), £80,594

Samit Chakrabarty, Ronaldo Ichiyama, Intl Foundn for Research in Paraplegia (Aug 2015), £93,000

Anastasia Zhuravleva, BBSRC (Jul 2015), £483,019

Alex O'Neill, MRC (Jul 2015), £249,822

Ade Whitehouse, Richard Foster, Cancer Research UK (Jul 2015), £201,034

Ronaldo Ichiyama, Jim Deuchars, Sue Deuchars, Wings For Life Spinal Cord Research (Jul 2015), £123,895

Martin Stacey and colleagues in FMH, MRC (Jun 2015), £426,475

Adrian Goldman, Sarah Harris, Roman Tuma, BBSRC (Jun 2015), £420,693

Elwyn Isaac, EU (Jun 2015), £238,915

Christine Foyer, BBSRC (Jun 2015), £160,401

Adrian Goldman, EU (Jun 2015), £116,331

David Brockwell, Sheena Radford, Innovate UK (Jun 2015), £113,378

Yoselin Benitez-Alfonso, EPSRC (Jun 2015), £93,672

Michelle Peckham, Peter Knight, Thomas Edwards, BBSRC (May 2015), £404,987

Michelle Peckham, Ed White, Peter Knight, BHF (May 2015), £208,184

Dave Westhead, Sheena Radford, Alex Breeze, BBSRC (May 2015), £51,021

Steve Clapcote, Vitaflo International Ltd (May 2015), £33,703

Les Firbank, Joe Holden, Pippa Chapman, NERC (Apr 2015), £388,726

Samit Chakrabarty, David Steenson, BBSRC (Apr 2015), £120,103

Paul Millner, Gin Jose, Sarah Aickin, DSTL Porton Down (Apr 2015), £63,407

Chris Hassell, David Lewis, The Physiological Society (Apr 2015), £6,900

Andrew Tuplin, Royal Society (Mar 2015), £15,000

Yoselin Benitez-Alfonso, Royal Society (Mar 2015), £14,770

Patricija Van Oosten-Hawle, Royal Society (Mar 2015), £13,960

Stuart Egginton, BHF (Mar 2015), £272,979

Keith Hamer, Department of Energy & Climate Change (Mar 2015), £58,066

Andrew Macdonald, Yorkshire Kidney Research Fund (Mar 2015), £41,171

Les Firbank, DEFRA Dept for Env. Food & Rural Affairs (Feb 2015), £20,000

Ian Hope, Marie-Anne Shaw, BBSRC (Jan 2015), £381,998

Paul Knox, BBSRC (Jan 2015), £5,000

Andrew Peel, BBSRC (Jan 2015), £359,077

Christine Foyer, BBSRC (Jan 2015), £408,334

Dave Westhead and colleagues in Experimental Haematology, Cancer Research UK (Jan 2015), £700,521

Mike McPherson, Christoph Walti, DSTL Porton Down (Jan 2015), £625,125

Sheena Radford, Mark Harris, Peter Stockley, Alan Berry, Alex O'Neill, Thomas Edwards, Adrian Goldman, Anastasia Zhuravleva, Wellcome Trust (Jan 2015), £443,015

Alison Ashcroft, Peter Stockley, Sheena Radford, Nicola Stonehouse, David Brockwell, Darren Tomlinson, BBSRC (Jan 2015), £340,937

Bill Kunin, EU (Jan 2015), £157,490

John Colyer, Leeds Teaching Hospitals Charitable Fund (Jan 2015), £40,000

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

Ryan Seipke, Royal Society (Nov 2014), £13,700

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

Alan Berry, Wellcome Trust (Oct 2014), £749,865

Les Firbank, Joe Holden, BBSRC (Oct 2014), £210,302

Darren Tomlinson and colleagues in Chemistry and Pathology, anatomy and Tumour Biology, Dr Hadwen Trusy (Oct 2014), £194,475

Paul Knox, EU (Oct 2014), £167,229

Martin Stacey and colleagues in Medicine & Health, Pfizer (Oct 2014), £90,453

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

Emmanuel Paci and colleagues in Chemistry, BBSRC (Sep 2014), £636,759

Andrew Peel, BBSRC (Sep 2014), £371,598

Lars Jeuken, Stephen Evans, BBSRC (Sep 2014), £333,684

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

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