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Research by Professor Abdul Basit's group at the UCL School of Pharmacy is leading to improved treatments for ulcerative colitis and other conditions through increased knowledge of the complex physiology of the gastrointestinal tract. Improved understanding of in vivo drug release and uptake has allowed development of three patent-protected technologies for improved drug delivery: PHLORALTM, for release of drugs in the colon, and DuoCoatTM and ProReleaseTM formulations designed to allow intact transit through the stomach followed by immediate release upon gastric emptying. These technologies are the subject of licences and ongoing development programmes, with PHLORALTM currently in phase III clinical trials. The impact is therefore the introduction of enabling technologies that have positively influenced the drug development programmes of pharmaceutical companies.
A routine test to screen for patients genetically disposed to serious side effects from treatment with thiopurine drugs has been widely adopted following research by the Academic Unit of Clinical Pharmacology at the University of Sheffield. The test has spared patients painful and potentially life-threatening sepsis, and saved the considerable associated treatment costs which have been estimated to be over £9,000 per patient for a 17 day hospital stay. It has also led directly to a change in clinical guidelines and recommendations in both the USA and UK.
In June 2013 Arena launched Belviq® (generic name: lorcaserin) as a novel drug treatment for obesity. Lorcaserin was approved by the Federal Drugs Administration (FDA — the USA drug regulatory body) on 26 June 2012 and scheduled by the Drug Enforcement Agency (DEA) in April 2013. The scientific rationale for the development programme for lorcaserin, which is a serotonin 2C receptor agonist, as a treatment for obesity rested, in significant part, on research carried out between 1997 and 2010 at the University of Sussex.
Clinical pharmacology studies conducted at Newcastle have led to optimisation of the administration of the chemotherapy drug carboplatin in children with neuroblastoma and other cancers. The research provided the rationale for carboplatin dosing based on patient renal function, with individualised dosing resulting in increased drug efficacy and reduced toxicity. This approach is now in widespread use in national and European treatment protocols, benefitting over 2,500 children. Similar drug monitoring approaches are being implemented for an increasing number of important drugs. Following a recent Newcastle-led national clinical trial, new dosing guidelines for the drug 13-cis retinoic acid have been adopted for high-risk neuroblastoma patients across Europe.
Researchers at Newcastle University discovered interactions in vitro between the widely prescribed cholesterol-lowering drug rosuvastatin and cyclosporine, and between rosuvastatin and gemfibrozil, at the liver transporter protein OATP1B1. Subsequent clinical trials showed that the interactions occurred in patients and slowed clearance of rosuvastatin from the body. The research findings not only had direct implications for the safe prescribing of rosuvastatin when it came to be marketed but also more far-reaching impact. US Food and Drug Administration and European Medicines Agency guidelines published in 2012 stipulate that pharmaceutical companies must investigate potential drug-drug interactions in the pre-clinical development phase of all candidates that bind that transporter.
Warfarin is an anti-coagulant drug prescribed to tens of millions of people in the UK and US who are at high risk of developing blood clots. Because individual sensitivity to warfarin varies in the population there is a risk of overdosing the drug and causing serious bleeding and even stroke in many people when starting treatment. In 1999 researchers at Newcastle University were the first to demonstrate a statistically significant link between a person's genotype and the appropriate dose of warfarin. In 2010 the US Food and Drug Administration (FDA) mandated inclusion of a table of dose recommendations based on genotype in the warfarin prescribing information leaflet accompanying the drug. Newcastle research forms the basis of the 2009 international standard algorithm for gene-guided dosing of warfarin. This approach has been adopted by large US medical centres and the FDA states that it will prevent 17,000 strokes a year in the US.
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 Abraham solvation parameter approach developed at UCL has become integral to the work carried out by drug discovery teams at [text removed for publication] and other major pharmaceutical companies, as well as research and development groups at international chemical companies including Syngenta and [text removed for publication]. It enables chemists to predict physicochemical and biochemical properties of chemicals, including drugs and agrochemicals, rapidly and efficiently, without the need to conduct time-consuming experiments. The method helps drug discovery teams to identify and optimise the most promising compounds, and often results in fewer compounds being made before a candidate is selected, saving time and resources. The approach has been integrated into software used for drug discovery [text removed for publication].
Professor Irving Kirsch has conducted a meta-analysis of both published and unpublished clinical trials of antidepressants (Kirsch et al., 2008). This analysis demonstrates that the effects of antidepressants are mostly placebo effects except with extremely severe depression. The analysis opened an international debate on antidepressant efficacy, influenced NICE guidelines for the treatment of depression (NICE, 2010), and led the scientific committee of the European Medicines Agency to reconsider its own approval of antidepressants (Broich, 2009). It also informed public opinion through widespread media coverage, and produced intentions to change prescribing habits among 44% of surveyed UK doctors. Public awareness of Kirsch's work is such that a class action has been taken against Pfizer, a large pharmaceutical company, and the Vatican has convened an international study meeting (14-15 June, 2013) to produce new recommendations for the treatment of depression.