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The research described below has made a major contribution to the clinical and preclinical development of endothelin receptor antagonists (ERAs) for the treatment of systemic sclerosis (SSc). As a result, ERAs are now standard management for pulmonary arterial hypertension related to connective tissue disease and specifically complicating SSc. This work has also led to the licensing of bosentan (one of the ERAs) for digital ulcer disease, a major non-lethal complication of SSc that impacts on quality of life, employment status and the major economic cost of SSc management. By 2012, more than 16,000 patients with SSc had been treated worldwide with these therapies, with numbers increasing every year.
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 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.
Research at the University of Nottingham has defined the clinical phenotype and management of lymphangioleiomyomatosis, a rare and often fatal multisystem disease affecting 1 in 200,000 women worldwide. The group has led the development and evaluation of new therapies and diagnostic strategies which are now part of routine clinical care. The research has underpinned the transformation of this previously under recognised and untreatable disease into a condition recognised by respiratory physicians, with international clinical guidelines, patient registries, clinical trials, specific treatments and a UK specialist clinical service.
Research conducted by Professor TM Cox has led to several advances in the management of lysosomal storage disorders; i) development of miglustat (Zavesca®); now available throughout the world (EMA and FDA approved) for adult patients with Gaucher's disease and throughout the European Union and five other countries worldwide for adult and pediatric patients with Niemann- Pick type C disease, ii) development of the potential successor eliglustat; now in Phase 3 clinical trials, iii) identification of a biomarker for Gaucher's: CCL18/PARC, now incorporated into NHS standard operating procedures for monitoring therapeutic intervention. His pre-clinical research into gene therapy for Tay-Sachs disease also helped establish the NIH-funded Gene Therapy Consortium and gain the FDA's pre-IND approval for clinical trials in 2013, which together have raised public awareness of this disease.
RVC research has helped transform differential diagnosis of canine heart disease, in first opinion veterinary practice, by demonstrating the value of peptide biomarkers and collaborating with diagnostics companies to ensure the findings have been translated into commercial assay kits available around the world. Contributions to major clinical trials have complemented this through improvements in canine cardiac disease treatment. This has benefitted dogs and their owners through improved and prolonged canine health; and has additionally delivered new guidance for professional practice, and economic value through increased therapeutic product sales and novel diagnostic services.
Impact: Health and welfare; policy in the form of national and international guidelines; diagnostic service; engagement with patient groups.
Significance: UoE-formulated diagnostic criteria adopted by the World Health Organisation (WHO), the European Centre for Disease Prevention and Control (ECDC) and US Centers for Disease Control and Prevention (CDC), enable reliable case ascertainment and longitudinal study of disease trends. The UoE Creutzfeldt-Jacob Disease Unit acts as an international reference centre for diagnosis. Case ascertainment has improved.
Beneficiaries: Patients with prion disease and their families, policy-makers, the NHS, charities.
Attribution: The UoE CJD Unit led the work with international collaborators.
Reach: Worldwide; diagnostic criteria are WHO-endorsed and have been adopted worldwide. Pooling of data across Europe has enabled assessment of 11,000 cases of sporadic CJD.
Researchers at the University of Manchester (UoM) have made a significant impact nationally and internationally on improving the outcome for children with acute lymphoblastic leukaemia (ALL) (~450 pa in the UK). The changes in clinical practice based on our research are now national standards of care for children with de novo and relapsed ALL in the UK and Ireland. Other international groups have adopted key findings from the results of our frontline trials. Our relapse protocol for childhood ALL underpins European and North American strategy for the management of relapsed disease.
Our biomarker research and underpinning technologies have commercially impacted upon the global R&D strategies of Unilever, Philips and Mars, realising new market areas for them, resulting in several million GBP invested in related R&D as well as "claim support" for products both in development and already available on shelves. Unilever have adopted biomarker outcomes as endpoints in clinical trials of new products, and Philips and Mars are developing with us saliva-based near-patient diagnostic tests for the human and small animal markets. We have also spun out two SME's: A) Oral Health Innovations (OHI) Ltd has developed online risk and disease analysis software for oral conditions, which was piloted, adopted and launched by Denplan, the UKs largest dental capitation plan operator (accessing 6500 dentists and 1.8 million patients), at the 2013 annual British Dental Association conference; and B) GFC Diagnostics makes SmokeScreen™ a non-invasive, sensitive and objective saliva test developed from our biomarker research at Birmingham University. Both technologies have already provided demonstrable social and commercial impact and given their uptake to date, will also deliver economic, environmental and health impacts.
Research at UCL into the use of tocilizumab has led to a new treatment and improved care for patients with juvenile idiopathic arthritis (JIA) and rheumatoid arthritis (RA) in adults. The drug is now approved around the world and recommended by NICE guidelines and is the standard of care in children with systemic onset JIA. It has been prescribed in every rheumatology centre in the UK for patients with severe RA. The impact of the drug on patients is to prevent disability, halt joint damage, improve function and increase quality of life.