The European Rare Kidney Disease Reference Network


Research Project

Project Title:

Towards novel therapies for a genetic congenital neuropathy affecting the bladder

Project Type:

Translational research

Disease group(s):

Renal malformations

Project Summary:

Science summary: The urinary bladder disease in urofacial syndrome (UFS), a devastating genetic congenital disease, is caused by abnormal differentiation of autonomic nerves that control bladder function; 2. Understanding cellular pathobiology of UFS will enable preclinical testing of novel therapies. Aims. 1. Determine whether autonomic neurons differ between wild type mice and those carrying mutated UFS genes (Hpse2 or Lrig2), and ameliorate defects by correcting aberrant biological pathways; 2. Demonstrate whether molecules encoded by UFS genes modulate autonomic differentiation of human pluripotent stem cells (hPSCs).
Experimental strategy. We will use complementary cell culture models: 1. Mouse pelvic ganglia as sources of bladder autonomic neurons; 2. Given the inaccessibility of similar tissues from people, hPSCs stimulated to differentiate towards autonomic neurons. Outcomes. We will have provided the first direct evidence that UFS molecules are involved in both the growth of bladder autonomic neurons in mice and in any type of human neurons. Additionally, we will have tested therapies to correct UFS defects ex vivo, as an essential prelude to future studies using UFS PSCs.
Lay summary: Peripheral neuropathies affect 2% of the general population. In these conditions, nerves which connect the brain and spinal cord to our muscles, skin and internal organs, become diseased. These conditions usually last for many years and they produce many unpleasant and crippling symptoms. Novel treatments to cure these conditions are urgently needed. People with one such disease, called urofacial syndrome, are born with abnormal nerves supplying their bladders and this can often lead to kidney failure in childhood. We discovered that some such people carry abnormal genes which normally make molecules essential for nerve growth and function. In this project, we will take the first steps towards curing urofacial syndrome nerve cells by feeding them with the normal molecules they lack.

Lead principal investigator(s):

Adrian Woolf, Manchester


William Newman, Manchester
Emma Hilton, Manchester
Susan Kimber, Manchester

Project Period:

01/2015   -   12/2018


Non-profit foundation

Project web page:

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