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Research conducted at King's College London into the mechanisms underlying hypoglycaemia unawareness in type 1 diabetes mellitus (T1DM) and novel technology for reducing the risk of hypoglycaemia has led directly to innovative changes in the management of diabetes. These include UK and worldwide development and dissemination of the government-recommended `Dose Adjustment for Normal Eating' (DAFNE) programme and on-going development of continuous subcutaneous insulin infusion (pump) therapy, now used by over 18,500 people with T1DM in the UK.
Measurement of hormones is essential to the understanding and diagnosis of endocrine diseases. White and her research group have developed unique antibodies that are widely used in diagnostic assays for adrenocorticotrophic hormone (ACTH) and related peptides, including the first and only kit for measuring pro-opiomelanocortin (POMC), the precursor of ACTH. These assays are used worldwide for diagnosis, decisions on treatment, monitoring for recurrence of tumours and prognosis in a number of patient groups with life-threatening endocrine disorders. Global sales of the ACTH Elecsys tests by Roche exceeded 6 million kits since 2008. AstraZeneca has used the POMC and ACTH assays in its drug discovery programmes in the cardiovascular and metabolic diseases therapy area. The antibodies therefore have had health impact in relieving suffering and in improving patient care, as well as commercial impact in worldwide sales of assays and influencing drug development strategies.
Research from the University of Brighton's Diabetes Research Group (DRG) has underpinned the translation of beta-cell replacement therapy into clinical application for the treatment of type 1 diabetes (T1D) to establish the world's first government-funded islet transplant service at six new UK islet-transplant centres. As a consequence, the first 65 successful islet transplants were performed, reducing the incidence of hypoglycaemic events by >95% and providing a life- changing therapy for patients. Through a leadership role in Diabetes UK, BONE integrated the interests of stakeholders and professionals to establish a new model for diabetes care. With the Juvenile Diabetes Research Foundation, in 2013 he launched in Parliament the first UK T1D Research Roadmap.
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.
In 2003, researchers at the University of Dundee identified the tumour suppressor LKB1 as a critical upstream activator of AMP-activated protein kinase (AMPK), which provided the first link between AMPK and cancer. Metformin, the front-line therapy for type-2 diabetes, was already known to exert its beneficial effects through AMPK. An interdisciplinary collaboration at the University examined the link between metformin and cancer, and reported in 2005 that diabetics taking metformin had a reduced incidence of cancer. The impact has been clinical trials worldwide testing the benefit of metformin for cancer treatment, and development of therapeutics by pharmaceutical companies targeting this pathway.
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 undertaken by Professor Frances Ashcroft at the University of Oxford and her collaborators at the University of Exeter has led to several hundred neonatal diabetes (ND) patients worldwide being able to switch from daily insulin injections to oral sulphonylurea tablet therapy since 2008. ND is a rare but potentially devastating monogenic form of diabetes affecting about 1 in 150,000 live births. Sufferers were previously assumed to have type 1 diabetes and thus were treated with insulin injections; sulphonylurea treatment has transformed their quality of life and led to marked health improvements. It has also ameliorated the mental and motor developmental delay that affects about a fifth of ND patients.
The treatment of patients with neonatal diabetes has been transformed by the research of Professors Sian Ellard and Andrew Hattersley at Exeter. Childhood diabetes usually presages a life-long requirement for insulin injections and a reduction in quality of life. This research revealed that ~50% of patients with permanent neonatal diabetes have mutations in a potassium channel regulating insulin secretion. A new diagnostic test was introduced and relevant patients were switched from insulin injections to oral therapy. As a result, patients in 77 countries across 5 continents now benefit from improved care, a better quality of life and reduced healthcare costs.
Metformin is now the most prescribed medication for type 2 diabetes worldwide. Pre - 1990 it received trivial use and was on the verge of withdrawal. Research at Aston (1993 - 1996) generated a new appreciation of its mechanisms of action and therapeutic potential. Aston research was reinforced with a concerted education programme for healthcare professionals, including high-profile reviews and treatment guidelines. We claim impact on health & welfare and health practitioners as Aston research has provided a foundation for improved care of type 2 diabetes patients on a global scale.