Interview with Nick Bishop, professor of paediatric bone diseases at the University of Sheffield, UK

Who are you and what is your relationship to OI?
My name is Nick Bishop and I am professor of paediatric bone diseases at the University of Sheffield in the UK. I’ve worked here for the last 25 years (nearly). When I first came to Sheffield, I set up a metabolic bone disease unit for children, which was the first such unit to be purely bone orientated in the UK. Most of the children that I looked after then, and over the following years, had OI. so I guess you could say that most of my professional life has been looking after children and families with osteogenesis imperfecta and undertaking research to try and improve outcomes for them.

You recently retired – is this a real retirement or are you continuing to work in secret?
I am “mostly retired“! I spend around one day per week working on the REMEDi4ALL demonstrator project, which is looking at the use of losartan, a medicine normally used to treat high blood pressure, in adults and older adolescents with osteogenesis imperfecta.

Tell us about the Remedi4All project!
The project that I am working on is one of four “demonstrator projects“ run by the REMEDi4ALL consortium. The overall consortium was funded by a large grant from the European Union –€25 million-and the coordinating group was developed from another European consortium called EATRIS. The main people steering, the consortium are Anton Ussi, Don Lo and Martin de Kort.

The whole purpose of the consortium is to create a system which can look at medicines that already exist but could be used for different conditions. So there are a lot of “work packages“, including one that focuses on the voice and needs of patients forming the consortium group. The demonstrator projects are all in a single work package.

For our specific demonstrator project, we are using centres in the UK and Italy only and to recruit 30 patients aged 16 and over to take losartan for 24 weeks. We are looking to find out whether using losartan reduces the speed with which bone is destroyed and then remade, which is normally increased in osteogenesis imperfecta.

Tell us about your career! How did it all start? When and how did you start working with OI?
I started off as a paediatrician interested in tiny babies and spent 10 years doing clinical practice and researching that area focusing on those born both small and early. As part of the original research, I did in that area, we needed to understand how the skeleton developed after that early life period and so I started measuring bone density in apparently normal children!

After a while, I started getting letters and calls asking if I could help with children who had got problems with bones, particularly fragile bones. I realised that I knew virtually nothing about bone disease in older children and ended up getting a fellowship to go to work with Francis Glorieux in Montréal for two years. That’s where I really learnt about osteogenesis imperfecta and brought that knowledge back to the UK.

Have you worked most as a clinician or researcher?
Since the time when I worked with premature babies, my effort has been spent equally working on clinical delivery and research to try and improve outcome, so I would say half and half!

Are there happenings that have made a special impression on you during your career?
I think there have been so many, that it will be difficult to pick out just one or two; every child with OI and every family has their own story, and I hope each one feels that they have been looked after as individuals by us in Sheffield. I think the time we spent as a family in Montréal was memorable, not just because of the clinical work, but because we made a huge number of friends who we go back to see on a regular basis.

Are there things in our career you regret?
Certainly; there are particular moments when I could have done a lot better but I think any doctor would tell you that. Overall, I guess my biggest regret is not being able to get the losartan study done in children, because we lost access to the liquid form of losartan which we wanted to use, because the manufacturer stopped producing it, just as the study was about to start.

What are most proud of during your career?
This might seem out of place in talking about OI, but I think the piece of research I’ve done that has made the biggest impact was the very first one in premature babies where we showed that aluminium contaminating their intravenous feeding solutions was causing brain damage. We managed to get the aluminium content of those feeding solutions lowered in legislation both in Europe and the United States as a result of the work that we did. This will have had a major effect on the neurodevelopment of thousands of premature babies in many countries over the last 20 years, so I am very proud of that.

Other highlights?
Setting up the paediatric metabolic bone disease clinic in Sheffield and growing and developing the team there; getting the highly specialised service for children with OI established in England with four centres providing multidisciplinary care; doing the study with risendronate, that showed a positive effect on reducing fractures in children with mild OI; being the first Centre in Europe to use the enzyme replacement therapy asfotase alfa for a child with hypophosphatasia; being the director of the first clinical research facility in a Children’s Hospital in the UK; my time as vice president for science and research at the Royal College of paediatrics and child health during the Covid pandemic which was pretty intense.

After OI2022 I felt a bit like a balloon after a party; it was such an enjoyable meeting for me, seeing so many friends and colleagues, all together in one place as the pandemic released its hold on us all – and then it all stopped!

During the years you have developed a close relationship to people with OI and the OI-community, especially the BBS. How has this influenced your way of thinking about OI?
I have always tried in my clinical work, as well as my research, to see things from the point of view of those who are “on the receiving end“ – both the children and their families; I think being able to work with organisations, such as the BBS, has simply reinforced that.

You have always been a champion for more patient involvement (PPI). Why is it important?
For me, PPI means listening to what patients want and making sure that it’s reflected in what I do whether that is clinical work or research. So, for instance, in the research study, we are doing, we have had patient input right from the very beginning in terms of the design of the study and thinking about what we can reasonably ask people to do. I expect that that involvement will continue throughout the course of the study, and in fact I would regard the ideal situation as being one of “co-production“. PPI is vital for research, because otherwise you lose that essential perspective which makes the study relevant and important for the OI individual.

Organisations can support in so many different ways – from directly contributing to the running of a study, to ensuring that the membership are aware of what is happening and can participate as individuals in things like trial steering committees and expert patient groups. Patient organisations can also act as a vital source of information for patients about studies and disseminate information from ongoing studies. This helps people understand what’s going on and encourages greater participation, whether or not that leads to actually being directly involved in the study itself.

What are the major things that have changed/developed in OI-research in the last 20 years?
I like to think that in the paediatric area we have led the way in trying to develop multidisciplinary services that are properly integrated for the care of children and their families. To me this has been the biggest advance in the last 20 years alongside the use of bisphosphonates. We are now in a period when new medicines may become available and that’s really exciting, but I will have to leave that to others to implement now I have retired.

Have most of the knowledge gaps in OI now been filled?
I don’t think most of the knowledge gaps have been filled yet. OI is such a complicated condition affecting not just the bones, but the muscles, lungs, heart and other tissues as well. We have a better understanding now of what is happening in the bones, but there is still plenty to find out about what is happening elsewhere in the body.

We’re living in exciting times – there have never been so many new treatments and therapies being investigated for OI as now. What are your thoughts on this? Are you optimistic we will find “the cure” or a more efficient therapy to alleviate symptoms?
Perhaps one day with gene therapy, but until we can correct the fundamental defect that produces abnormal structural proteins, like type one collagen – which is the problem for most people who have OI – any treatment will not be a cure, but simply something that treats the consequences of the underlying genetic problem. How far away is gene therapy? Difficult to answer because we’ve been promised that it’s coming for almost all the time I have been in clinical practice – so I suspect that it will be another 10 to 15 years at least.