Interview with Prof. James Bainbridge on his work in clinical trials

We spoke to Prof. Bainbridge – our co-lead in our Genomic Discovery and Therapeutics theme – about his motivations and work in clinical research:  

What first piqued your interest in the research space and clinical trials? 

It was a combination of factors, one of which was simple curiosity about how the eye works, how the eye is affected by disease processes, and how those change people’s lives for the worse. Then I discovered that with this knowledge I had the opportunity to potentially make a difference, by improving on the current management options that we have available and by developing novel interventions. It really was a combination of curiosity and the opportunity to make a difference to people’s lives. 

What stage of your medical career were you at when you took that leap? 

I was in training as a resident, then called SPR (speciality resident), I was midway through training in ophthalmology when I took some time out to do full-time research. This involved doing a PhD in a subject which combined my interest in microsurgery, which I was passionate about, with an opportunity to learn about molecular biology, which is essentially genetics. I had some idea about the potential importance and power of genetics, but I was wholly ignorant of how it works and how it could be used to make a difference to people. 

What have been your biggest milestone successes in research and what is your most recent? 

The biggest successes I’ve had have been in trials of gene therapy for children and young adults with severe genetic eye disease. These are people who have devastating conditions causing severe sight impairment and for which there are no treatments available. The prognosis for these people is unfavourable. I had the opportunity to contribute to research programmes where we were able to test gene therapies developed in the laboratory and apply those therapies to people with these conditions to find out whether it would make a difference. 

There are a couple of instances where we found that this approach can indeed improve outcomes. Around 20 years ago in a form of childhood genetic blindness, we found that their outcome was changed for the better. The therapy involved providing the gene RPE65, which was otherwise lacking to the retina of those individuals. We saw rapid improvements in aspects of their sight following gene therapy. That was very exciting. 

The most recent success we’ve had is in a condition which is similar but much more severe, affecting babies and young children. The condition is caused by a deficiency in the gene AIPL1. We found that surgery to provide the gene can improve the outcome for those young children in a way that’s really very dramatic. This showed that the approach could dramatically improve outcomes in young children with this more aggressive condition. These trials have helped demonstrate that this approach, introducing the healthy gene to the eye, can be helpful in people affected by genetic diseases.  

Although these diseases are quite rare, the hope and expectation is that with further development, similar approaches might be made available to people with more common genetic blinding diseases, and the technology might also be applied to people with other, non-genetic diseases that are even more common. 

What are the main challenges you face in the process of clinical trials? 

There are lots of challenges. One of the main challenges is designing ways to test new treatments in a way that is safe, reliable, and cost-effective. Developing trials that satisfy all these criteria can be very challenging, not least because of funding. We can be very confident about measuring the impact of a new treatment if we have lots of people to measure over a long time, but that’s very expensive. The challenge is to refine trial design to measure results confidently with as few participants as possible as rapidly as possible. 

How has the NIHR featured in your career? 

The NIHR has supported me enormously, and I don’t think I’m alone in owing a great deal to them. I’ve enjoyed the support of the NIHR Moorfields Biomedical Research Centre throughout my career, which has been crucial. In addition, I benefited from the award of an NIHR Research Professorship, which provided support for myself, other research staff and covered the costs of specific research studies. This was critical for the genetic treatment we most recently reported. 

What would you say to early career clinicians and researchers looking to work in the field? 

I advise people to follow what interests them most and use that as motivation and incentive. This is essential to maintain the determination and resilience needed to overcome challenges and achieve success. It’s great to have the opportunity to answer specific questions of intellectual interest that also have profound meaning and potentially wide-ranging value in terms of improving people’s lives. That combination can be very powerful. 

What do you see in the future of ophthalmic research and how do you fit into that future? 

The future lies in continuing to translate scientific findings into benefits for people affected by blinding diseases. I’m hopeful that recent advances in technology, data science, and artificial intelligence will accelerate research. For example, AI could be used to model experimental systems, support trial systems, and design new treatments. Importantly, AI may also be able to help identify the people most likely to benefit from new treatments and increase the success of trials in a reliable, safe, and cost-effective way. 

Further reading:

• Read about the RPE45 treatment 
• Read about the recent AIPL1 treatment  
• Prof Bainbridge Research Profile 
• NIHR Research Professorships