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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.
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.
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 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.
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 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.
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.
The Farndale group have identified fragments of collagen, synthesised and assembled in active, triple-helical conformation, for use as ligands to manipulate platelet function. As a result of this work, the fragment Collagen-Related Peptide (CRP) is included in British Committee for Standards in Haematology guidelines as a platelet agonist for the diagnosis of platelet defects. The group has also synthesised triple-helical collagen peptide libraries and used them to map binding of cells or proteins to collagen more widely. The peptides are made and distributed by the Farndale lab, generating income through sales and licencing, and are used internationally by companies and hospitals to develop diagnostics and for high-throughput drug discovery. Prof Farndale also acts as a consultant for companies developing diagnostics.
Fluorescence lifetime research since 1993 in Strathclyde's Photophysics Group led by Prof. David Birch contributed to the success of the University spin-out company IBH (Imhof, Birch, Hallam), and its successful merger with the £1Bn multinational company Horiba. The Strathclyde research has helped Horiba to be, since 2008, the market-leading supplier of fluorescence spectrometers, which comprise steady-state, lifetime and hybrid instruments. The commercial success of the company has led to economic benefits and employment. Through production of an improved spectrometry product range, the Strathclyde research has also facilitated multidisciplinary molecular and materials research globally, across Industry, Government and University sectors, bringing benefits to diverse disciplines such as life sciences, healthcare, chemistry, and nanotechnology.
Research on fluorescent PET sensors by de Silva at Queen's University Belfast was directly, and collaboratively, built into the Roche/Optimedical OPTI blood electrolyte analyser, which has had sales of US$50M in the past five years equating to 10 million sensors sold. The market for this sensor is global and it is used every day worldwide in hospital critical care units, ambulances, general-practice surgeries and veterinary care, often in life or death circumstances. The research, therefore, has led to both economic impact as well as significant health benefits.