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The diagnosis and treatment of patients with Maturity Onset Diabetes of the Young (MODY) has been revolutionised by the research of Professors Andrew Hattersley (FRS) and Sian Ellard at Exeter. Prior to this research, up to 90% of patients with MODY were misdiagnosed as having type 1 or type 2 diabetes. To address this, the team developed new tests and integrated these into routine diagnosis. They showed that patients could be stratified to achieve delivery of the most appropriate therapy and, as a result, as many as 15000 patients worldwide have now gained a better quality of life.
As a result of research from Oxford's Professor Andrew Wilkie, accurate genetic diagnostic tests are now available for over 23% of all craniosynostosis cases nationally and internationally, leading to improved family planning and clinical management of this common condition worldwide. The premature fusion of cranial sutures, known as craniosynostosis, is a common developmental abnormality that occurs in 1 in 2,500 births. Over the past 20 years, the University of Oxford's Clinical Genetics Lab, led by Professor Wilkie in collaboration with the Oxford Craniofacial Unit, has identified more than half of the known genetic mutations that cause craniosynostosis and other malformations of the skull.
Professors O'Rahilly and Farooqi were the first to identify monogenic causes of severe childhood obesity, leading the way for identification of additional genetic causes by their group and others. Their research led to the development of diagnostic tests for these conditions, which are now an accepted element of clinical guidelines around the world. This work led to the understanding that inherited disorders of appetitive drive can underlie human obesity which has altered attitudes to obesity and had an impact on the management of families with these conditions. Their research also led directly to a highly effective therapy for congenital leptin deficiency which reverses the severe obesity associated with this condition and associated endocrine and immunological deficiencies. This treatment is now available throughout the UK and in specialist centres worldwide.
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.
Our research has had impact on the activities of practitioners and their services, health and welfare of patients, on society and on public policy. New diagnostic tests for genetic deafness have been introduced, and healthcare guidelines and professional standards adopted through our investigation of the aetiology of childhood-onset hearing loss. Disease prevention has been achieved by our research on antibiotic-associated deafness, public awareness of risk to health and hearing has been raised, and we have increased public engagement through debate on scientific and social issues. We have also influenced public policy on ethics of genetic testing for deafness with our research resulting in improved quality, accessibility and acceptability of genetic services among many hard-to-reach groups (deafblind, culturally Deaf, and the Bangladeshi population of East London).
Identification of MUTYH by researchers at Cardiff University as the first gene causing autosomal recessive colorectal cancer led to international adoption of MUTYH genetic testing in the management of familial colorectal cancer and thereby to global improvement in genetic counselling and colorectal cancer prevention. Since 2008 MUTYH gene testing has been introduced progressively and is now provided by at least 84 European state and commercial diagnostic laboratories. Commercialisation of testing in North America via a licence to Myriad Genetics Inc. generated income of approximately $5M between 2008 and 2011 and licence fees and royalties to date of £331,947. Thus we claim impacts in health and commercial benefit, the financial beneficiaries being Myriad Genetics and Cardiff University.
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.
Neuroblastoma is a paediatric cancer that arises from the sympathetic nervous system. The average age at diagnosis is 18 months and the disease accounts for approximately 15% of all childhood cancer-related deaths. Determining optimal treatment for individual patients is crucial for increasing chances of survival and for reducing side effects of chemotherapy and radiotherapy. Newcastle-led research identified unbalanced 17q gain as the most common segmental chromosomal abnormality (SCA) in patients with neuroblastoma; this was present in more than 50% of patients. Gain of 17q is now one of the key SCAs used to determine treatment for patients in a European neuroblastoma trial and in UK treatment centres. Newcastle research also led to the development of a simple diagnostic test for the detection of the main SCAs in neuroblastoma.
Although individually infrequent, rare diseases collectively are a major health burden, particularly for individuals who suffer with conditions that are not routinely diagnosed or have no effective care pathways. Through the work of Professor Tim Barrett, the University of Birmingham is internationally recognised for translational research in rare inherited diabetes and obesity syndromes. This has had major impacts on patient care through gene identification for devastating multi-system syndromes; development of a unique international diagnostic testing service combining molecular testing with international clinical expertise; European reference centre status for three NHS highly specialised multidisciplinary services; and leadership of the European Registry for rare diabetes syndromes. Our national and international leadership for these previously poorly-served conditions has enabled sharing of best clinical practice, including development of clinics for Wolfram syndrome across the world.
Understanding and finding treatments for rare disease represents a major challenge across medicine. We have shown this is possible for rare muscle channelopathies and our work has directly benefited the lives of patients. Our 15 year basic research programme has elucidated the genetic architecture and identified new disease mechanisms for these disabling muscle conditions. We also determined the true disease frequency through the only UK epidemiology study. We translated fundamental research into new DNA-based diagnostic testing and electrophysiological diagnostics for rapid and reliable diagnosis. Our research led directly to our centre being commissioned by the NHS (£6m) as the only UK centre for diagnosis and management and we established the UK NHS national genetics channelopathy reference laboratory. We have built the world's largest genetically stratified patient cohorts which allowed us to lead the first international randomised controlled trial. This trial showed clear efficacy of a reprofiled mexiletine. This led to a successful European orphan product status application for this indication and national treatment guidelines.