Scientists from the University of Sheffield are part of an international collaboration to develop a new class of drugs to treat a common genetic kidney disease, which is a major cause of kidney failure.
Working with Glasgow-based biotech company Mironid and colleagues in the United States (U.S.), the Sheffield researchers have carried out successful laboratory tests of a compound developed by Mironid to treat autosomal dominant polycystic kidney disease (ADPKD), a hereditary, progressive disease which affects over 60,000 people in the United Kingdom (U.K.) and around 12 million people worldwide. ADPKD is caused by a genetic fault that disrupts the normal development of kidney cells and causes cysts to form inside the kidneys.
The cysts, which are like fluid-filled blisters, grow and eventually destroy normal kidney tissue causing the kidneys to stop working properly. This leaves patients needing life-saving treatments, such as dialysis or a kidney transplant.
ADPKD cells, cysts develop and grow because they express higher than normal levels of a ‘messenger molecule’ called cyclic AMP (or cAMP). One of the many known functions of cAMP is to tell cells when to divide and when to secrete fluid.
The new compound discovered by Mironid activates is an enzyme called PDE4, whose natural role is to break down cAMP.
Professor Albert Ong, a consultant nephrologist and professor of renal medicine who led the experiments conducted at the University of Sheffield said: “Drug development usually focuses on looking for ways to block molecular and chemical processes, not switch them on, so this is a rare mode of action. As a researcher, it’s very exciting to be involved in the early stage development of a completely new class of drugs.