A human slice model to understand the role of fibrosis in children with bladder exstrophy

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Bladder exstrophy is a condition in babies where the bladder and front of the abdomen fail to develop properly, which leaves the open bladder exposed on the front of the tummy at birth. Surgery for affected children is only available in Manchester or Great Ormond Street (GOS) in the UK but outcomes are poor, even with the best care in these specialist centres: many are permanently incontinent with frequent urine infections and have sexual dysfunction in later life. The applicant, Mr Johal, leads exstrophy surgery at GOS and has a unique research background with a PHD focussing on normal and abnormal function of the muscles in the bladder. He has shown that most of the expected bladder muscles are replaced by scar tissue in exstrophy. This occurs via a process called fibrosis, which is also implicated in many other conditions; hence there are a number of new drugs being developed to treat fibrosis which have not yet been tested in exstrophy. Part of the abnormal bladder is removed during routine exstrophy surgery, and this will be used by Mr Johal to test whether fibrosis can be stopped (or even reversed) by these drugs, in collaboration with Professor David Long (Institute of Child Health) who has successfully undertaken similar experiments in the kidney. Taken together, Mr Johal's unique background, access to exstrophy samples and drive to improve outcomes combined with support from Professor Long's innovative laboratory team, this is a timely opportunity to increase understanding of bladder exstrophy and test new therapies that may be used clinically in future.