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Original basic research on melatonin receptors undertaken at the Rowett Institute, University of Aberdeen, and funded by the Scottish Government, provided the opportunity for Servier pharmaceuticals to develop a new line of therapeutics for depression.
The company exploited Rowett know-how and invested in new research to develop a new line of compounds and to understand their structure-function relationships. This work enabled the development of melatonin analogues for clinical trials and ultimately led to the development of melatonin compounds for treatment of circadian related disorders.
One (S20098) was identified as having positive effects for disrupted circadian rhythms and beneficial outcomes for patients with depression. S20098 (also known as Agomelatine) was launched after EU authorization in 2009 as a novel anti-depressant drug called Valdoxan®. Today Valdoxan is an award winning anti-depressant drug recognised for its novel mechanism of action and few side effects. Valdoxan is the only anti-depressant drug to be brought to the market in the last 10 years. In summary, supported by investment from industry research undertaken at the University of Aberdeen contributed to the development of a novel antidepressant drug that provides a new clinical intervention with advantages over previously available antidepressants that will make a significant impact on the health and well-being of those afflicted by depression.
Research conducted at the University of Bristol since the late 1990s has pioneered the development of over 60 chemical probes that are selective for individual ionotropic and metabotropic glutamate receptors. The development of these probes has led to numerous commercial impacts, including: the establishment of two companies, which both sold during the assessment period for a combined value of £85 million, and sales revenue for global providers of biochemicals. This research has also stimulated considerable industry investment in drug development.
Research by the School of Pharmacy has underpinned the development of fluorescent ligand probes that have opened-up new pathways in drug discovery. These ligands have been commercialised through the formation of the spin-out company CellAura Technologies Ltd, and have been made globally available through a number of distributer agreements. Customers include pharmaceutical companies (e.g. Pfizer, AstraZeneca), drug discovery biotechs (e.g. Addex, Heptares) and drug discovery technology providers (e.g. CisBio). These ligands provide alternatives to the use of radio-ligands, giving more informative and safer solutions for industrial drug discovery. This has, for example, enabled: a new direction in G protein-coupled receptor research at Novartis Pharmaceuticals UK Ltd; validation of Promega Corporation's new drug-binding assay; and superior performance in the establishment of cell lines at inSCREENex GmbH.
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.
Fluorescent ligand technologies developed by Professor Hill and Dr Briddon in the Pharmacology research group, in collaboration with Professor Kellam in the School of Pharmacy, permitted biophysical analysis of G-protein coupled receptors (GPCRs) at the individual cell and molecule level for the first time. The technologies have been commercialised through the spin-out business, CellAura Technologies (and their distributors Abcam, Sigma-Aldrich and others), generating revenues and making the products available to researchers and drug discovery communities worldwide. Custom product developments with global pharmaceutical companies and drug screening reagent providers have generated further partnership revenues and technology benefits. Nottingham-trained researchers are now employed worldwide, broadening the technology's impacts.
Members of the Pharmacology Research Group identified hitherto unknown properties of G protein Coupled Receptors (GPCRs): that ligands can signal differentially through both G-protein-coupled and β-arrestin pathways. This led to the concept of GPCR `biased signalling' and development of fluorescent reporters to quantify β-arrestin signalling. These discoveries have been adopted widely by the pharmaceutical industry, attracting R&D investment and collaborative research funding, to drive discovery of new drugs operating through `biased signalling'. The commercial opportunity has also been exploited by screening reagent providers and contract screening organisations. These discoveries will ultimately produce better drugs to treat GPCR-based diseases to improve human health.
Research by Professor Kevin Fone in the Neuroscience group has established and characterised rodent models of CNS disorders that have been instrumental in validating several 5-hydroxytryptamine (5-HT) receptors as therapeutic drug targets to treat learning and memory dysfunction in humans. Specifically, animal studies to validate the 5-HT6 receptor for cognitive impairment in Alzheimer's disease (AD), depression and schizophrenia have resulted in R&D investment in drug discovery programmes by several global pharmaceutical companies. Consequent advances in healthcare benefits (current and potential) are also summarised.
Based on electrophysiological research conducted at the University of Warwick from 2000, Neurosolutions was founded as a spin-out company in 2001. As well as developing its own novel compounds, Neurosolutions provides specialised translational biomedical research services to the biotechnology and pharmaceutical industries to facilitate preclinical drug development of novel strategies to treat neurological disorders. In 2005, Neurosolutions floated on the Australian Stock Exchange (ASX) as Neurodiscovery to support the clinical development in-house of two compounds (both are patent-protected): NSL-043 for neuropathic pain (which completed 2 phase I studies in 2008-2009) and NSL-101 for dental pain (which completed phase II trials in 2009-2010). In 2010, Neurosolutions expanded its operations to Montreal, Canada. Neurosolutions is a profit- making contract research organisation with 15 full-time staff based in the UK and in Montreal, has annual revenues averaging £1.4M per annum and has earned around £7.5M in contracts from the biotechnology and pharmaceutical industries since its launch.
Professor of Pharmacology David Colquhoun's extensive work on receptor mechanisms and ion channel function has armed him with the pharmacological, statistical, and analytical skills essential to the sophisticated evaluation of evidence in the medical sciences. Over the past ten years, he has applied these skills to assess the validity of public policies, especially on the use of alternative therapies as clinical treatments. Having built up evidence-based arguments that alternative therapies, such as homeopathy and reflexology, are ineffective at best and dangerous at worst, he was able to achieve the nation-wide closure of university courses in these subjects. He has also ensured that the homeopathy information available on the NHS Choices website is not misleading. Through his widely read blog, DC's Improbable Science, Colquhoun educates the public in skills of evidence evaluation.
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.