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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).
Research at the University of Manchester (UoM) has led a step-change in respiratory care for airway disease from oral to novel inhaled therapies targeted at asthma and chronic obstructive pulmonary disease (COPD) patients worldwide. UoM researchers carried out >250 studies, partnered industry to deliver >15 new inhaled drug formulations to market and were the first to test novel CFC-free inhalers. UoM led the development of global guidelines that influence better diagnosis and management of airways diseases. Through leadership within the Montreal Protocol since 1995, UoM researchers coordinated the safe global transition to CFC-free inhalers for ~200m patients with asthma and COPD, whilst protecting the ozone layer and climate.
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.
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.
Lung cancer is the commonest cause of cancer-related mortality worldwide. The University of Manchester (UoM) Lung Cancer Group has generated insights that underpin new standards of care in the treatment of advanced, metastatic small cell (SCLC) and non-small cell lung cancer (NSCLC), contributed to the results required for licensing of new drugs and secured approval for new treatment regimens now in routine clinical use internationally. Key contributions include an increase in survival of 23% in advanced NSCLC with the use of chemotherapy and doubling one-year survival from 13% to 27% in patients with incurable, extensive stage SCLC by the use of prophylactic cranial irradiation. The Group's research has impacted on outcomes for thousands of patients worldwide.
15m people have a stroke each year worldwide. In England alone, stroke generates direct care costs of £3bn and a wider economic burden of £8bn. Service users report high levels of unmet need in relation to cognitive dysfunction (e.g. concentration). Improving cognition was the number one priority agreed by users and providers (James Lind Alliance, Lancet Neurology 2012). Research led by the University of Manchester (UoM) underpins recommendations in several recent clinical guidelines for stroke management and rehabilitation in the UK and internationally. Our 2012 aphasia trial and qualitative study made key contributions to the recommendations in the recent NICE (2013) and Intercollegiate Stroke Working Party (2012) guidelines. UoM-led Cochrane reviews (e.g., neglect, apraxia, perception) have directly influenced recommendations in guidelines produced by the Scottish Intercollegiate Guidelines Network, the European Stroke Organization and the Australian National Stroke Foundation.
When anti-TNF therapies (which block tumour necrosis factor) were first licensed in 1999 only a few hundred patients with rheumatoid arthritis had received them, most for relatively short periods of time. Although the drugs represented a major breakthrough, `real-world' effectiveness and safety were unproven. Research at the University of Manchester (UoM) has addressed this knowledge gap and has successfully refined the ways in which anti-TNF drugs are used around the world, leading directly to more effective prescribing and improved patient outcomes. The research has also provided strong evidence that women do not need to discontinue anti-TNF treatment prior to conception.
Research at the UCL Institute of Child Health (ICH) has led to the successful treatment of children with primary immunodeficiency diseases for whom there was little chance of "cure" by the only other possible means: haematopoietic stem cell transplantation (HSCT). Beginning in 2002, we have treated 32 patients with four different primary immunodeficiency disorders. In total we have treated 12 patients with severe combined immunodeficiency (SCID-X1), 13 patients with adenosine deaminase deficient severe combined immunodeficiency (ADA-SCID), 5 patients with chronic granulomatous disease (CGD) and 2 patients with Wiskott-Aldrich syndrome (WAS). Most of the patients have been successfully treated and are at home, off all therapy. We are now starting to develop this technology to treat a wider range of related disorders.
People who develop psychosis (1% of population) typically experience lengthy delays (months to years) before treatment. Researchers at the University of Manchester (UoM) established a concrete and significant association between delay in treatment of the first episode of psychosis and outcome. We demonstrated that outcome of psychosis could be improved considerably if these lengthy delays were reduced. This research influenced policy and practice in the UK and abroad. Policy changes included the establishment of early psychosis teams dedicated to early detection and treatment (50 in England alone). Practice changes included amendments to clinical guidelines in the UK and abroad that now require clinicians to respond urgently to a first episode of psychosis. These changes to clinical practice have increased the proportion of patients with a short DUP from 55.6 to 77.4%.
Although, by definition, individually rare, the cumulative burden of `rare disease' is significant, with as many as 3m affected individuals in the UK. The University of Manchester (UoM) has an exceptional record in rare disease gene identification, with 29 such genes defined since 1993. This research paved the way for clinical diagnostic testing for patients and their families, demonstrating the immediate translational impact of gene discovery. The research has resulted in a reduced diagnostic burden for patients and health services and has enabled the provision of more effective counselling. Testing for genes identified at UoM is now offered in more than 140 laboratories in more than 30 countries worldwide. More than 1,100 patients have been tested for mutations in TCOF1, BEST1, IRF6, SAMHD1 and C9ORF72 in UK NHS laboratories alone.