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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 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.
Between 1996 and 2013 researchers at Swansea University evaluated service initiatives and changing professional roles associated with the management of patients with debilitating gastrointestinal disorders. This work showed the clinical and cost effectiveness of two main innovations: open access to hospital services for patients with inflammatory bowel disease; and increased responsibility for nurses, particularly as endoscopists. Our evidence has had a broad, significant impact on: national policy through incorporation in NHS strategies, professional service standards and commissioning guides; service delivery through the provision of increasing numbers of nurse endoscopists and the wide introduction of nurse-led open access to follow-up; and patient care, as documented in sequential national audits in 2006, 2008 and 2010.
Dialysis has revolutionised the management of End Stage Kidney Disease (ESKD), but the benefits of this invasive, demanding treatment may not be clear-cut for elderly, frail patients with other serious comorbidities. University of Hertfordshire and East and North Hertfordshire NHS Trust researchers have led the development of Conservative Management, an alternative to dialysis for some patients, providing multidisciplinary support and careful symptomatic management until death. The research shows that quality of life is maintained, survival may not be significantly compromised, and preferred place of death is more often achieved than for counterparts on dialysis. Conservative Management programmes have been adopted across the UK and elsewhere, influencing the care of many patients.
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.
Congenital myasthenic syndromes (CMS) are inherited neuromuscular disorders caused by defects at neuromuscular junctions, which are often a result of acetylcholine receptor gene mutations. A subset of CMS patients (around 14% in the US and Europe) have limb-girdle myasthenia (LGM). This disease can be highly disabling with symptoms including increasing weakness of skeletal muscles. As a result of collaborative work between Newcastle and Oxford, it was determined that many LGM patients have a mutation of the Dok-7 gene (unrelated to the acetylholine receptor), and do not, therefore, respond to standard CMS treatments. Since then, a number of additional mutations have been discovered, and genetic testing is now available for the majority of known LGM-causative genes. Crucially, Dok-7 patients, and those with other non-receptor related mutations, can now be diagnosed accurately and treated effectively, with ephedrine and salbutamol (in the US, albuterol). This significantly improves these patients' quality of life by enabling them to walk and breathe unassisted.
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.
Chronic granulomatous disease is a rare but very serious inherited disorder of the immune system that leaves sufferers vulnerable to potentially fatal bacterial and fungal infections. Researchers at Newcastle University demonstrated very high survival and cure rates following bone marrow transplantation for the disease and good quality of life for successfully transplanted patients. This led to a change in national clinical policy, and doctors at both specialist disease centres in the UK now recommend transplantation to families where previously they would not have done so. In the five years prior to 2008 there were only 11 transplants for chronic granulomatous disease in the UK and in the following five years, 36 transplants. 32 children are alive and cured of the disease.
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.
Impact: Health and welfare; public health studies in Sri Lanka and clinical trials in a cohort of 35,000 pesticide self-poisoning patients have led to the withdrawal of high-dose pralidoxime as a WHO-recommended treatment and bans of three toxic pesticides in Sri Lanka.
Significance: Resultant changes in clinical practice and pesticide regulation have saved 3000 lives in the last four years in Sri Lanka alone; in the rest of Asia many times this as local guidelines and practice have changed.
Beneficiaries: Patients and communities, healthcare providers, policy-makers.
Attribution: Studies designed and led, with international collaborators, by Michael Eddleston, UoE.
Reach: International, particularly Asia, changes in WHO and international guidelines on pesticide use.