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More than three million people are in pain at any one time in the UK, with inadequate analgesic treatment because of side-effects or lack of drug efficacy. By identifying roles for the voltage-gated sodium channel subtypes Nav1.7 and Nav1.8 in peripheral pain, our research has had a significant impact on the clinical understanding of human pain disorders and on the commercial development of selective analgesics with fewer side-effects. We have developed and disseminated several transgenic mouse lines which are widely used by the pharmaceutical industry. Through media appearances, we have also increased public awareness of the physiological basis of pain.
As a result of our discoveries of a new splice variant (ASIC1b) and a new member (ASIC4) of the ASIC family, and elucidation of their roles in pain caused by tissue acidity, several pharmaceutical companies are now working on ASIC-targeted analgesics and one company has been set up specifically to focus on this work. ASIC-related therapies for a wide variety of conditions are now in clinical trials, with substantial patient involvement. Our work has allowed new therapeutic applications to be conceived for already existing prescribed compounds, and for naturally-occurring compounds, that act on ASICs. Thus, our research on ASICs has had clinical and commercial impact.
The Glasgow Composite Measure Pain Scale (CMPS) has provided the first validated pain questionnaire for the rapid assessment of acute pain in dogs in surgical and clinical settings. Developed by the University of Glasgow School of Veterinary Medicine, the scale aids clinical decisions on appropriate pain relief intervention and has been freely downloaded by over 3,000 clinical users since its launch in 2008. In addition, it has been used extensively by veterinary healthcare companies to successfully obtain regulatory approval for analgesic drugs and in marketing support materials. The University of Glasgow researchers have been instrumental in developing international pain guidelines with the World Small Animal Veterinary Association, which represent more than 180,000 veterinarians worldwide, and has thereby promoted awareness of pain management in companion animals.
A high quality clinical trial, systematic reviews and meta-analyses performed by a team at Brunel University have directly informed key international clinical practice guidelines, policies and on the management of low back pain and neuropathic pain and have been cited by users (NHS Trusts: Addenbrookes) in response to such guidelines. In this way our research is directly informing clinical practice.
Professor Geoffrey Burnstock and colleagues' establishment of the molecular structure of the P2Y class of receptor led to the cloning of several receptors within this class, which are increasingly seen as therapeutic targets for a variety of disorders. Indeed, drugs acting at these receptors are already improving patient health worldwide by reducing the risk of thrombotic events in people suffering from myocardial infarction or ischaemic stroke (via P2Y12 receptor antagonists) and by relieving the symptoms of dry eye disorder (via P2Y2 receptor agonists). Burnstock and colleagues also cloned the P2X3 receptor which mediates pain information, and P2X3 antagonists are being developed as novel analgesics. As well as clear clinical benefits, these drug developments are associated with substantial economic and commercial benefits.
Research by Maria Fitzgerald's group in the Department of Neuroscience, Physiology & Pharmacology has provided fundamental biological knowledge of the development of pain pathways in the human fetus that is recognised all over the world. As a direct result of her published research, she co-authored a report from the Royal College of Obstetrics and Gynaecology on clinical recommendations for practice in fetal medicine and fetal termination. Published in March 2010, this report provides authoritative, evidence-based recommendations for medical practitioners, abortion advisory groups and patients, and consequently determines clinical practice throughout the UK. The recommendations impact upon a large number of women; in 2011 there were 196,082 abortions in England and Wales.
Eight per cent of all live births in the UK are preterm. Many of these infants spend time in special care, receiving an average of ten painful procedures per day of hospitalisation. Analgesics are administered to infants on an ad hoc basis and evidence of their efficacy has relied upon observations of behaviour and indirect physiologic responses. Fitzgerald and Slater at UCL have pioneered neurophysiological measurement of pain activity in the human infant brain, based upon Fitzgerald's developmental pain research. Using this measure, they have carried out the first ever randomised clinical trial of neonatal analgesic efficacy using a quantitative neural outcome.
About one in 1,000 children are born deaf, and nearly half of all children born deaf have a mutation in one of a number of different genes. Work at Sussex in 1998 on the composition of the tectorial membrane, an extracellular matrix of the inner ear, led to the identification of TECTA as a deafness gene. Because of our research, mutations in TECTA are now known to be a cause of autosomal dominant non-syndromic hearing loss, with 288 affected patients from 51 different families identified worldwide, to date accounting for ~1-2 per cent of all autosomal dominant non-syndromic hearing loss. Critically, TECTA is now one of 60 deafness genes included in genetic tests for hereditary deafness.
The University of Glasgow's Centre for Rehabilitation Engineering (CRE) has developed strategies and products that have influenced clinical practice in Spinal Cord Injury (SCI) worldwide. The CRE refined the concept of using Functional Electrical Stimulation (FES) for cycling and abdominal stimulation and defined its benefits to patients by establishing the nature of the medical benefits of the technology.
Working with clinical partners in the Southern General Hospital and Hasomed GmbH, the CRE co-developed FES products that are now used routinely in clinical rehabilitation. Hasomed sell ~500 units p.a. across the world, for use at home, in fitness centres and in SCI clinics to maintain health and wellbeing, thereby reducing patient morbidity and increasing their life expectancy.
Neuro-feedback, utilising a Brain Computer Interface for the treatment of pain associated with SCI, has also been developed into a clinical reality and a limited clinical trial has now shown its efficacy.
Research led by Dr. Peter Richardson in the Department of Pharmacology led to the development of an A2A adenosine receptor antagonist (istradefylline) for the treatment of Parkinson's disease. In 2001, Dr Richardson founded the spin-out company Cambridge Biotechnology (CBT) to develop these drugs. A pH-sensitive adenosine A2A receptor agonist is now being developed for the treatment of neuropathic pain, with one product licensed for use in Japan in 2013 (Nouriast). Small-molecule leptin mimetics as potential anti-obesity drugs were also developed, initially by CBT and since 2009 by Astra Zeneca following acquisition of the research programme. CBT has undergone a number of high-value acquisitions, by Biovitrium, Proximagen, and most recently Upsher-Smith. It continues to operate as a wholly-owned subsidiary, employing 30-35 people from 2001 to the present.