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Neurons in the central nervous system do not normally regenerate following injury, due in part to the presence of `inhibitory' molecules that actively prevent the growth and/or collateral sprouting of axons. King's College London scientists identified myelin associated glycoprotein (MAG) as the first myelin inhibitory molecule and demonstrated that inhibition of MAG function with a monoclonal antibody promotes axonal regeneration. They have gone on to promote MAG and its receptor (called the NgR1) as druggable therapeutic targets. Their discovery has led the UK's largest pharmaceutical company — GlaxoSmithKline — to develop monoclonal antibodies to MAG and a second myelin inhibitor as clinical drug candidates. The anti-MAG therapeutic successfully completed Phase I and II clinical trials in humans for stroke during 2008-2013.
The sport and exercise science team at Southampton Solent began its work only in 2007, with little or no previous scholarly history. The new team focussed on the area of strength and conditioning within the area of sport, exercise and health. The overarching approach to strength and conditioning training methodology defined in the work of Fisher et al (2011) is momentary muscular fatigue (MMF) whereby training is undertaken to maximal exertion. Using MMF the research team have demonstrated public benefit, and thus interim impact, through improving performance within client groups suffering from chronic low back pain (CLBP). Thus, we hope to show interim impact and reach using this methodological approach improving performance in those with CLBP.
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.
Alzheimer's disease (AD) presents society with one of its biggest challenges, yet despite the investment of billions of dollars there are only two classes of drug approved that have minimal benefit in patients. Scientists at King's College London have implicated dysregulation of retinoid signalling as an early feature of the disease and identified the retinoic acid receptor (RAR) family as an attractive drug target. They have gone on to design and patent protect novel orally available RARα selective agonists and demonstrated that they have the potential to restore many of the deficits reported in AD patients. Advent Venture Partners has provided funds to establish a new UK biotechnology company, CoCo Therapeutics Ltd, in partnership with the Wellcome Trust and KCL, to progress this KCL research into the development of a new treatment for AD.
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.
The cell adhesion molecule N-cadherin has been shown to be required for the survival of cancer cells, their metastasis and the formation of new blood vessels in solid tumours, however, cell adhesion molecules like N-cadherin were generally not considered to be "druggable." Scientists at King's College London have contributed to the development of a "peptide-pipeline" of novel N-cadherin antagonists, including the cyclic HAV peptide (N-Ac-CHAVC-NH2), also now known as Exherin and/or ADH-1, as a "first-in-class" N-cadherin antagonist. This compound was granted FDA organ drug designation for Melanoma in 2008 and successfully completed a number of phase I and II clinical trials, with an additional clinical trial currently recruiting. The demonstration that N-cadherin peptides can be used to treat cancer has changed the perception of what is possible and opened up new clinical and commercial opportunities.
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.
Newcastle University research has changed policy and practice relating to the provision of pain relief to rodents and rabbits. This has impacted on up to 35 million animals worldwide during the REF period. Having established the under-use of analgesics in laboratory rodents, Newcastle researchers developed objective pain scoring systems. These established that analgesics should be administered to rodents and rabbits, and that the efficacy of this treatment should be assessed objectively. The research resulted in changes to policy statements, institutional policies (both academic and industrial) and individual research worker practices in the USA, Canada, Australia, Europe and the UK. This has produced clear benefits to the welfare of animals used in biomedical research, helps to satisfy public concerns that animals used in research should experience the minimum pain and distress, and improves scientific outcomes of research, since pain is an uncontrolled experimental variable, that can adversely affect study results.
The Pain Research Group (PRG) is a research team within the Centre for Health and Social Care Research (CHSCR). The PRG's research programme in chronic pain management encompasses a range of robust methodological approaches to achieve better patient outcomes with local, national and international impact. The PRG has adopted a dual approach to investigating the treatment of chronic pain, incorporating psychological factors with the application of neuromodulation techniques. This has led to significant improvements in patient outcomes and patient satisfaction surveys demonstrate excellent, positive results. The research has had significant influence on clinical practice at national level, underpinning recommendations for best practice issued by the British Pain Society in relation to spinal cord stimulation and intrathecal drug therapy. It has also contributed to NICE's clinical guidelines on the implementation of spinal cord stimulation and influenced clinical decision making through the NHS evidence database. At an international level, our research has contributed to three sets of guidelines issued by the Polyanalgesic Consensus Conference: inflammatory mass, intrathecal drug therapy for chronic pain and recommendations for reducing mortality and morbidity of intrathecal drug therapy. The reduction of morbidity and mortality in intrathecal drug therapy is of particular significance as the reduction of harm and unnecessary complications in healthcare is of high concern to healthcare organisations worldwide.
Adolescents (and their families) in the UK and around the world are now better able to cope with chronic pain because of the unique work carried out at the University of Bath Centre for Pain Research (BCPR), directed by Professor Christopher Eccleston.
The BCPR produced the first multidimensional `one-stop' tool to assess the impact of pain on children's lives, which has now been adopted in at least 12 countries. Pioneering treatments from Bath have influenced therapeutic approaches worldwide.
The Bath team also manage the evidence base for chronic pain, giving access through the Cochrane Library, advising internationally on clinical service development and improvement.