Pathophysiology of Congenital Bladder Disorders
Research type
Research Study
Full title
The pathophysiology of lower urinary tract disorders in children with congenital anomalies
IRAS ID
239994
Contact name
Navroop Johal
Contact email
Sponsor organisation
Great Ormond Street Hospital for Children
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
This study aims to characterise the pathogenesis and genetics of urinary bladder contractile dysfunction associated with congenital anomalies that include: bladder outflow obstruction in boys (posterior urethral valves), bladder exstrophy (caused by incomplete formation of the abdominal wall and bladder) and spinal cord defects (spina bifida) that cause bladder problems such as neuropathic bladder. Surgical correction of the developmental abnormality, soon after birth and in later years of childhood, continues to improve. However, advances in enabling the urinary bladder to function normally have been far slower to be realised. In consequence poor urine voiding, leading in some cases to eventual kidney damage, remain very common these patients.
A central similarity between these conditions is deposition of connective tissue in replacement of muscle within the bladder. The aim of the study is to examine four aspects through separate experiments that together will advance our understanding of bladder dysfunction in these patients. Those aspects are 1) what are the different cellular signalling pathways that contribute to bladder dysfunction 2) what are the differences in biomechanical properties in these tissues as compared to normal bladders 3) what are the differences in genetics between these patient’s bladder tissue and normal bladder tissue and 4) can novel hormonal treatments such as relaxin, reverse some of the dysfunction seen in these patient’s bladder tissue.
If these basic questions can be answered this will allow the identification of therapeutic drug targets (such as relaxin) to boost existing muscle function and/or decrease the formation of non-muscular tissues. Both of these strategies can in principle be pursued if the underlying pathophysiology can be characterised.
REC name
London - Surrey Research Ethics Committee
REC reference
18/LO/0394
Date of REC Opinion
19 Apr 2018
REC opinion
Further Information Favourable Opinion