Here’s a simple summary of the work – read on for more detail.
Slowed movement of digested food through the gut frequently leads to constipation and blockages that require hospital treatment and even surgery in people with cystic fibrosis. Existing treatments are limited in their success. This centre will investigate using licensed drugs and peptides to reduce the amount of sodium and water absorbed by the gut lining, to improve the movement of matter through the digestive system. To do this, they will use lab-grown mini-guts called ‘organoids’. The best treatment will then go through a clinical trial to assess its potential.
Now for the detail!
Slowed movement of digested matter in the gut of people with cystic fibrosis (CF) frequently leads to constipation and blockage (called distal intestinal obstructive syndrome [DIOS]), which requires hospital treatment and occasionally surgery. The cause of DIOS is not known, but is associated with dehydration and the thickening of bowel contents resulting from inherited defects in the CFTR protein, which controls the movement of chloride (one part of salt) in cells that line the gut. Attempts to use drugs to restore CFTR function in the gut have had only limited success for most cases of cystic fibrosis. An alternative approach to increase the fluidity of contents moving through the gut and prevent DIOS is to reduce sodium and water absorption by gut-lining cells.
How the SRC will work
Led by Professor Soraya Shirazi-Beechey at the University of Liverpool, this SRC will test this idea using licensed drugs and peptides, which reduce sodium and water absorption by gut-lining cells. The project will apply cutting-edge techniques to CF mouse models (mouse test subjects altered to simulate the conditions observed in humans with CF), intestinal biopsies and lab-grown mini-guts (called ‘organoids’) from people with CF afflicted by DIOS.
For the best DIOS therapy identified, a large clinical trial will be planned to robustly test this new treatment, thereby informing the development of an effective new treatment for gut blockage in people with cystic fibrosis.
What are the aims?
This research aims to:
- address CF gastrointestinal disease, which frequently causes intestinal obstruction requiring hospitalisation and sometimes surgery;
- use knowledge and understanding of how intestinal fluid is regulated to propose an innovative new strategy to rehydrate the intestine.
- test drugs that are safe and already in clinical use, meaning that, if laboratory experiments are successful, clinical trials will likely begin sooner than for a completely new treatment; and
- plan a large multi-centre clinical trial as part of our programme of research to robustly evaluate the best therapy for intestinal obstruction that we identify. If successful, the research will lead to an effective evidence-based treatment for intestinal obstruction in CF that will work for everyone with CF, regardless of their genotype.
Lead Principal Investigator (PI): Professor Soraya Shirazi-Beechey (University of Liverpool)
- Professor David Sheppard (University of Bristol)
- Professor Hugo de Jonge (Erasmus University Medical Centre)
- Professor Ursula Seidler (Hannover Medical School)
- Professor Christopher Taylor (Sheffield Children’s Hospital)
- Dr Louise Robson (University of Sheffield)
- Professor Michael Wilschanski (Hadassah University Hospital, Jerusalem)
- Dr Richmond Muimo (University of Sheffield)
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