Title: Pre-clinical testing of new therapeutic treatments for cystic kidney disease
Funder: Action Medical Research

Abstract: Background_x000D_ Cystic kidney disease is an inherited disease which occurs when there is a fault in a gene controlling the development of cilia. Cilia are tiny hair-like structures that protrude from the surface of most animal cells like antennae. Like antennae, they receive signals from other cells and their surroundings, and help the cell behave appropriately. When cilia do not form properly, this leads to a range of developmental disorders called ciliopathies. Ciliopathies almost always have kidney cysts as a feature, and are a major cause of chronic kidney disease in both children and adults. At any one time, around 5,000 patients in the UK are receiving treatment, either dialysis or a kidney transplant, as a result of an inherited kidney disease. However, there are few effective treatments that can prevent or slow the progression of cystic kidney disease._x000D_ _x000D_ The research project_x000D_ The lack of drugs to prevent or treat cystic kidney disease means that existing medicines, approved to treat other conditions, are being evaluated as potential treatments. These researchers have identified a number of approved medicines and other small molecules that improve cilia formation and function. In this project, they will test if these compounds are effective in cell-based models of ciliopathies and kidney cysts, including kidney cells taken from patients. For the most effective compounds, they will then run safety and efficacy tests in more complex animal models to pave the way for clinical trials. The advantage of developing established medicines to treat new conditions is that their pharmacological and safety profiles are already well understood, and therefore the research could quickly move forward into a first clinical trial within 5 years. This study may identify several potential much-needed new treatments for cystic kidney disease that could then be entered into in a more extensive drug development programme._x000D_

Lay abstract: Background_x000D_ Cystic kidney disease is an inherited disease which occurs when there is a fault in a gene controlling the development of cilia. Cilia are tiny hair-like structures that protrude from the surface of most animal cells like antennae. Like antennae, they receive signals from other cells and their surroundings, and help the cell behave appropriately. When cilia do not form properly, this leads to a range of developmental disorders called ciliopathies. Ciliopathies almost always have kidney cysts as a feature, and are a major cause of chronic kidney disease in both children and adults. At any one time, around 5,000 patients in the UK are receiving treatment, either dialysis or a kidney transplant, as a result of an inherited kidney disease. However, there are few effective treatments that can prevent or slow the progression of cystic kidney disease._x000D_ _x000D_ The research project_x000D_ The lack of drugs to prevent or treat cystic kidney disease means that existing medicines, approved to treat other conditions, are being evaluated as potential treatments. These researchers have identified a number of approved medicines and other small molecules that improve cilia formation and function. In this project, they will test if these compounds are effective in cell-based models of ciliopathies and kidney cysts, including kidney cells taken from patients. For the most effective compounds, they will then run safety and efficacy tests in more complex animal models to pave the way for clinical trials. The advantage of developing established medicines to treat new conditions is that their pharmacological and safety profiles are already well understood, and therefore the research could quickly move forward into a first clinical trial within 5 years. This study may identify several potential much-needed new treatments for cystic kidney disease that could then be entered into in a more extensive drug development programme._x000D_

Research activity codes: 5.1 PHARMACEUTICALS
Health categories: RENAL AND UROGENITAL