Mini-MUSIC: A successful example of paediatric patient-informed translational research

Written by Michelle Wilson

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Children and young people are neglected in clinical research and particularly in translational research, even in common diseases. As a chronic, complex polygenic disease, there is no cure for Inflammatory bowel disease (IBD; Crohn's disease (CD) and Ulcerative colitis (UC) which affects almost 1% of the all-ages UK population. Under 10% of all people with IBD in the UK are diagnosed as children or young people (less than 17 years of age: paediatric-onset IBD or PIBD). Children with IBD experience distressing and debilitating symptoms with disease complications such as fatigue, undernutrition, impaired quality of life, particularly mental well-being, and ability to attend school and have unrestricted family, social and sporting life. Research led in Child Life and Health in IRR has shown that Scotland has among the highest PIBD incidence and prevalence rates in the world.

It is clearly wrong to neglect children and young people in research. They have the same rights as adults to high-quality evidence-based investigations, care and therapies. Our PIBD patient and parent engagement events in recent years demonstrate that children and young people have their own opinions, often different from those of clinical teams or parents, and so we moved on to let these patient voices help shape our research in PIBD.

Even with our previous successful Scotland-wide PIBD research led by Prof David Wilson and colleagues, the numbers of PIBD cases are an obstacle to fund and deliver high-quality research studies. Our solution within IRR was to team up with Dr Gwo-Tzer Ho’s IBD Science group to design imaginative harmonised studies in children and young people AND adults – ‘all-ages’ IBD research. Our first translational study is the Mini-MUSIC project, expanding Gwo-Tzer’s Helmsley Trust-funded MUSIC trial in adults into all-ages IBD research, but with paediatric-specific design, aims and methods. We obtained significant funding from Edinburgh Children’s Hospital Charity (ECHC) to employ a research fellow (Dr David Wands) and research associate (Michelle Wilson) and to commence Mini-MUSIC in our Scottish PIBD centres in Edinburgh, Glasgow, Aberdeen and Dundee.

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In IBD, one of the most important treatment goals is endoscopic healing of the bowel - where there is no evidence of active inflammation seen during endoscopy. This leads to best prognosis and reduces complications. Ileocolonoscopy is the gold standard for monitoring but carries with it the need for bowel preparation (unpleasant for many children and young people), poor tolerance, associated complications, need in PIBD for day case attendance missing education and parents or carers not being at work, and use of finite NHS resources. Currently, we do not have reliable non-invasive markers that predict active inflammation. Mini-MUSIC is studying damage-associated molecular patterns (DAMPs) as ‘biomarkers’ to aid PIBD diagnosis, to predict bowel-wall inflammation, responses to drugs and side effects, and as mechanistic biomarkers to identify IBD cases with a key mitochondrial dysfunction phenotype in participants aged 6-17 years. Time spent listening to members of our all-ages IBD patient panel highlighted how patients face many challenges with fluctuating energy levels and extreme fatigue. This PPI feedback drove our inclusion of fatigue (including use of paediatric fatigue scores) as a key study outcome, along with PIBD-specific quality of life measures to explore wellness. Following our start in Edinburgh on 5^th January we have in 10 weeks already recruited 20% of our planned cohort of 60 PIBD participants into this 12 month longitudinal study.

However, with relatively few PIBD patients, we realised that successful translational research needs to involve the research active PIBD centres throughout the UK in a research network. The great enthusiasm and positive feedback from PIBD patients and families who came from across the UK to our large PIBD patient and family engagement day at the EICC in September 2022 demonstrated the strong appetite for participation in translational research beyond Scotland. Driven by this patient engagement feedback we successfully applied for and obtained funding from Crohn’s & Colitis UK to expand our successful Mini-MUSIC project from Scotland to UK-wide, and which will start later in 2024. Further to Mini-MUSIC’s results, hopefully a functioning UK-wide PIBD translational research network will also be its legacy.