Scientists are developing a revolutionary new stem cell therapy to treat a rare and life-threatening disease that leaves newborn babies unable to function without invasive surgery, thanks to a collaboration between the University of Sheffield, UCL Great Ormond Street Institute of Child Health, and Queen’s University Belfast.
The research, which brings together world-leading experts in stem cell biology, gastrointestinal tract physiology, statistics and health economics, aims to provide a permanent cure for children born without a functional "second brain" in their digestive tract.
For children born with Hirschsprung disease (HSCR), the act of digesting food is a life-threatening challenge because they are born without the vital network of nerves in the bowel known as the enteric nervous system. Currently treatments involve surgically removing the non-functional section of the gut but many patients continue to suffer from life-long infections and bowel dysfunction.
The £2.7 million UKRI-funded project, led by Dr Anestis Tsakiridis, has developed a method to ‘grow’ missing nerves from human stem cells. This new Sheffield-developed technique can produce the cells needed to build vital nerves in just six days - almost twice as fast as existing methods.
The team has demonstrated that their lab-grown cells are not only effective at restoring gut function in patient tissue samples but are also "off-the-shelf" ready. This means the cells can be frozen and safely transported, a vital step in ensuring the therapy can be delivered to patients in hospitals across the UK and beyond.
Dr Anestis Tsakiridis (University of Sheffield) said "This grant provides us with a unique opportunity to take our stem cell therapy for this devastating disease one step closer to the clinic. We are incredibly grateful to the MRC for supporting this work, which allows us to move our cell production method out of the lab and toward real-world application".
These "Sheffield-grown" cells can then be put to the test by the clinical team at UCL Great Ormond Street Institute of Child Health. Drawing on their deep expertise in paediatric surgery and patient care, the London-based team led by Dr Conor McCann have already shown that these cells can successfully integrate into human tissue and restore the rhythmic contractions necessary for a healthy gut. This partnership ensures that the laboratory science is grounded in real-world clinical need and guided by the lived experiences of families affected by the condition.
Dr McCann (UCL Great Ormond Street Institute of Child Health) said: “The award of this funding will provide a step change in allowing us to bring our stem cell-based treatment closer to the clinic.
“We hope that by bringing together the expertise of different groups across the UK we can drive this project towards a clinical trial that will hopefully benefit children with Hirschsprung disease and their families.”
To ensure the therapy can then be integrated into the NHS, experts from UCL and Queen’s University Belfast will develop the health economic framework for the project. Early modelling suggests that a one-time cell therapy could be a highly cost-effective alternative to the long-term burden of repeat surgeries and specialised care currently required by patients.
The research team will also be working closely with families affected by Hirschsprung disease and the charity Guts UK to ensure they prepare for the next phase of the project, which will focus on safety testing ahead of first in-human clinical trials.
While the initial focus is on Hirschsprung disease, the researchers believe this technology could eventually be adapted to treat other debilitating gut disorders such as achalasia and gastroparesis - potentially reversing permanent damage once thought untreatable.