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Research conducted at the University of Bristol between 1994 and 2013 has led to major commercial impact through industry investment in cancer therapies that target a family of transporter proteins (MCTs) identified and characterised by Professor Halestrap and his colleagues. Halestrap has worked directly with AstraZeneca, a leading global biopharmaceutical company, to integrate the Bristol-based research into their own research programme to elucidate the mode of action of a group of novel immunosuppressive agents that target MCT1. Subsequent ongoing collaborations have underpinned AstraZeneca's development of these drugs for cancer chemotherapy, with clinical trials of their compound AZD3965 underway, as well as investment in a new cancer drug discovery programme targeting the MCTs.
University of Bristol researchers at the Bristol Heart Institute (BHI) have pioneered the development and clinical take-up of the novel technique of off-pump coronary artery bypass (OPCAB) surgery. Over ten clinical trials and several large cohort analyses have assessed the impact of this technique on elective and high-risk patients. The results have shown that it is as safe as the conventional coronary artery bypass grafting (CABG) technique that uses a cardiopulmonary bypass pump and cardioplegic arrest. Most importantly, however, OPCAB significantly reduces the risk of post-operative complications, and reduces morbidity and mortality. It also uses less hospital resources, reducing time in intensive care and length of hospital stay. In 2011 (the last year for which data are available), 20% of CABG operations in the UK were carried out with the OPCAB technique and it has had significant take-up overseas (for example, 18% of CABG operations in the US and 21% in the EU in 2010). NICE has recommended the safety and efficacy of OPCAB surgery.
Every year in the UK, 150,000 heart attacks are caused by coronary artery occlusion (blockage); worldwide, the figure is 17 million, according to the World Health Organization (WHO). Since 1993, the Leicester Interventional Cardiology group has been at the forefront of research to determine how best to manage such patients. Its findings have been incorporated into official UK (2008), European (2008, 2012) and US (2008) guidelines and have helped to change the way coronary heart disease and heart attacks are treated, with the number of patients treated with primary angioplasty doubling between 2008 and 2011. By guiding service provision, supporting industrial innovation and informing clinical practice, the Unit has contributed to improved healthcare and outcomes for thousands of heart patients. Overall, one-month mortality according to European figures has fallen from 15% to 4% between 2008 and 2013.
Research at the University of Manchester (UoM) has changed the landscape of medical care and research in fungal infections internationally. The impacts include: the world's first commercialised molecular diagnostic products for aspergillosis and Pneumocystis pneumonia (£10m investment); pivotal contributions to the preclinical development (£35m investment), clinical developments and registrations of 3 new antifungals with combined market share of ~$2 billion; one (voriconazole, 2012 sales >$750m worldwide) now first line therapy for invasive aspergillosis with improved survival of 15-20%; and internationally validated methods to detect azole resistance in Aspergillus (an emerging problem partly related to environmental spraying of azole fungicides for crop protection).
Since 2010, infants around the world have been saved from death or severe disability as a result of research conducted by Professor Marianne Thoresen and her team at the University of Bristol. Translational research conducted between 1998 and 2010 by the Thoresen group showed that mild cooling of newborn children who had suffered a lack of oxygen during labour and delivery reduced death and disability by over 50%. Extensive publication on this treatment and practical training for neonatal staff, led by the Bristol team since 2008, has transformed the management of neonatal brain injury. By 2010/11, therapeutic cooling had been adopted as standard treatment throughout the developed world, saving thousands of children from death or severe disability, including cerebral palsy and epilepsy. Therapeutic hypothermia also saves the NHS and UK families about £200 million/year in care and compensation costs.
40% of all cancer patients, who are cured of their disease, receive radiotherapy as part of their treatment. The number of cancer cures could be increased if the application of radiotherapy could be improved. Research at the University of Manchester (UoM) has: led the way in identifying, validating and exemplifying the value of predictive/prognostic biomarkers of response to radiotherapy; and demonstrated, in clinical trials, the therapeutic efficacy of combining molecularly targeted agents with radiotherapy. Further, the pharmaceutical industry has incorporated these concepts into drug development programs, accelerating clinical drug development, and thus saving them time and money.
Imperial College preclinical studies guided the desired selectivity profile for long-acting muscarinic receptor antagonists (LAMA). Binding, functional and clinical studies from Imperial laboratories were the first to demonstrate the long duration of tiotropium bromide (Spiriva®) in human tissue, and confirmed its long duration of action in patients and established it as the first-line treatment for chronic obstructive pulmonary disease (COPD). Tiotropium has had a beneficial impact on the management of COPD and is incorporated into the major international treatment guidelines. It improves symptoms, reduces exacerbations and mortality, and provides a cost-effective therapy. Imperial have also produced the first pre-clinical and clinical data for the next LAMA in development (glycopyrrolate, Seebri®), which has recently been marketed. Our profiling of tiotropium has also led to the development of several novel LAMA.
Hull-based research on critical systems thinking has been used for public, private and community benefit in Australasia, due to pivotal partnerships with the International Centre for Complex Project Management in Australia and the Institute of Environmental Science and Research (ESR) in New Zealand. Benefits include: the reconciliation of economic and environmental imperatives in NZ water management, valued at NZ$1.7bn of economic growth; NZ$6.2m for ESR projects serving government clients; improved stakeholder consultation on NZ science investments; the development of new systems thinking capacity in the Victoria Department of Primary Industries (Australia); and 5% cost savings in key Australian defence procurements.
For stroke patients and any patient undergoing surgery the time period from diagnosis to treatment is a major factor in clinical outcomes. Research carried out at the University of Warwick has led to the development of sensors that can be used to measure, in whole unprocessed blood, diagnostically useful analytes that can be used to select the best therapeutic treatments. Point-of- care diagnosis and prompt referral to an appropriate care pathway, facilitated by the use of biosensors, will result in efficiency savings for healthcare professionals and the NHS in the long- term, and will also improve patient outcomes. To commercialize these biosensors, Sarissa Biomedical Ltd was founded in 2002, as a UK-based spinout from the University of Warwick. Sarissa sells, around the world, microelectrode biosensors fabricated by a unique enzyme deposition technology protected by patents filed in 2004 and 2008 by the University of Warwick. The diagnostic sensors are based on technology that incorporates Ruthenium Purple and use a sol-gel coating to entrap enzymes on a microelectrode. Sarissa is pursuing human trials of its biosensors as diagnostic tools in two main areas: stroke, and trauma with associated sepsis.
The development of the chemistry of Selectfluor® (F-TEDA-BF4) has resulted in this Manchester-discovered reagent becoming the world's most widely used commercial electrophilic fluorinating agent to introduce fluorine into a range of pharmaceuticals and agrochemicals. Annual worldwide production is ca. 25 tonnes and sales estimated to be US$7.5m. Selectfluor is used in the synthesis of fluticasone, a fluorinated corticosteroid which is the active ingredient in GSK's Advair ($3.6bn sales in 2010) used in the treatment of asthma and chronic obstructive pulmonary disease symptoms; top 25 selling drugs Flixonase, Flixotide, Flonase, Flovent HFA and Advair Diskus which had total sales of over $17bn between 2009-2012.