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Basic and translational research undertaken since 1993 by UCL Virology has defined the natural history and pathogenesis of cytomegalovirus (CMV) infection and disease. As a consequence of our work, rapid diagnosis and pre-emptive therapy are now available worldwide for this important infection. We have provided a national reference service for strains of CMV resistant to current antiviral drugs and for diagnosis of congenital CMV infection.
Sustained research by the University of Oxford's Mahidol Oxford Tropical Medicine Research Unit in Thailand (MORU) has been the driving force behind the current World Health Organization recommendations for the management of acute and chronic infection in patients with melioidosis. This research has motivated improvements in treatments and provided new strategies to identify at-risk populations, enabling clinicians to make early diagnoses. Melioidosis is a major cause of severe illness in parts of Southeast Asia and there are increasing numbers of cases in India, China, and Brazil.
Starting from a mechanism-based hypothesis, Alastair Compston and colleagues in Cambridge have led the academic development of Alemtuzumab as a highly effective therapy for relapsing-remitting multiple sclerosis through Phase 1, 2 and two Phase 3 trials (1991-2012). The impacts to date are demonstration of the importance of the therapeutic `window of opportunity' in treating multiple sclerosis; a product licence in the European Union (September 2013) for the commonest potentially disabling neurological disease of young adults; expansion of the work-force in industry to develop and market this initiative; and an estimated several-fold increase in revenue to the University of Cambridge (and other beneficiaries) from total royalties of £18.6M from 1997 to date.
Research conducted by Professor Tim Goodship and co-workers at Newcastle has had a profound effect on the prognosis for patients with atypical haemolytic uraemic syndrome (aHUS). By engaging in research on the genetic factors underlying the disease they developed an understanding of the molecular mechanisms responsible. Identifying that the majority of patients with aHUS have either acquired or inherited abnormalities of the regulation of complement (part of the immune system) led to the establishment of a UK national service for genetic screening and treatment with the complement inhibitor eculizumab. As eculizumab is now available to patients in England, the progression to end-stage renal failure can be prevented and patients already on dialysis will soon be successfully transplanted.
Research on Congenital Adrenal Hyperplasia (CAH) at the University of Sheffield has resulted in both health and commercial impacts. The research has led to a new drug treatment, Chronocort®, being developed for CAH. Chronocort® has been tested in CAH patients with the positive outcome of improved disease control.
Commercial impact arose from the creation of a spin-out company, Diurnal Ltd, in 2004 which has raised investment of £3.8M since 2008, including £0.4M from pharmaceutical industry sources, and (as an SME partner) a €5.6M Framework 7 grant to develop a paediatric treatment for CAH. Diurnal has created five new jobs and has contracts with six UK companies worth £2.7M.
The human influenza A (H5N1) infection emerged in China in 2003 and quickly spread throughout Asia, killing more than half of those infected. Researchers at the Oxford University Clinical Research Unit in Vietnam (OUCRU) provided rapid information to the World Health Organization (WHO) on the pathological and clinical features of H5N1 infection in humans, as it emerged in Vietnam. The WHO used this front line information to inform recommendations for the investigation, diagnosis, management, and treatment of H5N1 globally, ultimately reducing mortality by up to 19%.
Research from the University of Nottingham on aminoglycoside antibiotics in cystic fibrosis (CF) has changed clinical practice and improved patient safety internationally. There are over 70,000 people with CF worldwide. Most require frequent and prolonged intravenous courses of aminoglycoside antibiotics (which can cause kidney damage) to treat chronic lung infection with Pseudomonas aeruginosa. This infection may lead to respiratory failure and death. Our research has influenced national and international guidelines, and changed practice, such that once-daily aminoglycosides (less toxic to the kidneys) are now used. We have also stopped the use of gentamicin, in favour of less toxic aminoglycosides.
The University of Liverpool (UoL) research identified corticosteroid treatment for more than 3 consecutive months as a risk for serious sepsis in Crohn's disease and an indicator of poor practice; there are 115,000 Crohn's disease patients in the UK. Following this, national audits of Inflammatory Bowel Disease (IBD), also under UoL leadership, showed reduction in inappropriate long term steroid from 46% of Crohn's disease patients in 2006 to 21% in 2010. These audits led to widespread adoption of National Service Standards for the Care of Patients with IBD. Death and hospital readmission rates for IBD patients were subsequently significantly reduced.
Jayne's team have co-ordinated a sequence of randomised clinical trials, that have defined the standard of care for ANCA vasculitis treatment and shaped national and international guideline statements, NHS national commissioning guidance and an on-going NICE assessment. Together with Ken Smith his group have pioneered the use of the B cell-depleting agent rituximab, in vasculitis, contributing key evidence that led to its licence approval (USA and EU) for this indication. Ken Smith's group supported by Jayne's clinical team have discovered novel therapeutic biomarkers, patented and being assessed in Phase II clinical studies, that promise to deliver "personalised medicine" in this and related conditions. These activities have harmonised the management of vasculitis, are improving patient outcomes, and have provided a resource for on-going scientific and clinical studies.
Research at UCL firmly established tacrolimus as the optimal calcineurin inhibitor to use in immunosuppressive regimens following liver transplantation. Compared to ciclosporin its use improved graft survival by 6% and patient survival by 7%. Assuming 550 liver transplants per year in the UK since 2008, we can estimate that, with 90% of patients treated with tacrolimus and 10% ciclosporin, tacrolimus-based immunosuppression has resulted in 165 grafts and 192 lives being saved during the period 2008-13.