How would you explain your research?
Some people develop changes in the way they perceive their sensory ‘worlds’ when they have some form of illness. In this sense we’re most familiar with pain – it develops when we damage our bodies as a protective sense. However, in some people pain can start in this way but then doesn’t go away when they heal. Our research centres on why some people get chronic pain and others don’t, by looking at the way neurons behave using animal models of pain.
One less familiar area in which senses change is in taste and smell perception, but very little attention is paid to this as there are very few ways to treat it, even though it can have considerable impact on peoples’ lives.
How does your research benefit society?
Our work on chronic pain currently involves identifying new ways in which we might alter the way neurons signal pain, and how we could stop it. We’ve identified such new targets for analgesia, and we’re working on drugs that might be developed into new painkillers.
Taste and smell could be possible indicators, or biomarkers, of illness. Smell changes very early in Parkinson’s disease and is being developed as a diagnostic tool. Similarly we’ve proposed that taste perception could be a possible diagnostic in mood disorders, such as depression.
What inspired you to pursue this area of research?
People find it funny that as a qualified dentist I research pain – the profession has a bit of a reputation for an interest in pain, or more commonly inflicting it. I started working in the area as an undergraduate when I intercalated a degree in neuroscience in my dental degree.
As far as I know, I was the first dentist in the UK to do this as I was on one of the first neuroscience degrees in the country. I then started work with some really inspirational scientists – Ainsley Iggo, Alan Brown, Arthur Duggan, Danny McQueen, Sue Fleetwood-Walker and many others at the University of Edinburgh – and despite doing other things along the way I couldn’t leave pain research behind.
Tell us about your work on vascular endothelial growth factor.
VEGF is a family of proteins normally found in the body. They’ve been known for a while because of their function in making new blood vessels grow, which we need when we’re healing, but that can also be a problem for us as well.
Most work on VEGF has centred on the growth of solid cancers, which need to stimulate new blood vessels to grow and get enough oxygen, otherwise tumours couldn’t grow much larger than a few cubic millimetres. VEGF is also really important in eye diseases such as wet age-related macular degeneration (AMD), where damage to the eye and sight loss is caused by new vessels growing in the retina – these can leak and result in bleeding and damage, and eventually loss of sight. Injections into the eye that many people with AMD now have, block the effects of VEGF.
The many members of the VEGF family are fairly closely related, and are made by a process called alternative mRNA splicing – this is sort of like old film editing where the messenger RNA that will be translated into protein has pieces cut out of it, and is then spliced back together.
We are looking at how different VEGF splice variants affect neurons – VEGF can protect them from damage and block pain in animal models. Our collaborations with Dave Bates and Nick Beazley-Long at Nottingham, and Richard Hulse at Nottingham Trent University are exploring how spinal cord and brain blood vessels, VEGF and neurons interact to cause pain in inflammation. We’re also looking at splicing inhibitors in our academic research to see if blocking splicing could be used as an analgesic.
And this research led to you starting a company?
Exonate Ltd was founded when we moved to Nottingham, by Dave Bates, Steve Harper (a consultant renal physician in Bristol), myself and our CEO Dr Catherine Beech.
The company is focused on eye disease but we have been able to use some of the work the company has done to enable us to also look at pain. I’d been very sceptical about any contribution of VEGF to pain or analgesia for quite a while, so it just shows how open minds can lead to new discoveries.
The company focuses on the development of new drugs that inhibit the splicing of the VEGF-a family as a treatment for eye disease. Importantly we’re also developing new ways of delivering those drugs using eye drops rather than eye injections, which is the current treatment for wet AMD.