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Research at UCL on human haemolytic anaemias known as the `hereditary stomatocytoses' has improved diagnosis of these conditions, meaning that patients now avoid unnecessary and potentially life-threatening splenectomies, and inappropriate investigation and treatment for raised potassium levels. Identification of a common single nucleotide polymorphism that causes apparently normal red blood cells to leak salt when cooled (as is normal procedure with donated blood) has raised awareness of this issue in the NHS Blood and Transfusion service, with the result that individuals with this condition have been identified among existing donors, and work is underway to develop a screening method to exclude such individuals from donating blood that cannot be stored safely. Finally, the research has facilitated diagnosis of the recessive metabolic disorder phytosterolaemia by blood count, allowing these individuals to be given appropriate dietary treatment to control their cholesterol levels.
King's College London (KCL) research has made a major contribution to improving the quality of life for patients who have anaemia linked with chronic kidney disease. Studies undertaken by KCL researchers established that intravenous iron supplementation was required in anaemic patients with advanced kidney disease, in whom oral iron therapy was ineffective, and defined the best regimes for administration of intravenous iron. Subsequent KCL work on drugs that stimulate production of red blood cells (erythropoiesis) defined the target levels of haemoglobin to aim for in chronic kidney disease patients. Most recently, KCL researchers made the key discovery that the novel drug peginesatide for the first time enables the rescue of patients who develop a rare and potentially fatal reaction against erythropoietin (which is the commonest treatment for anaemia in chronic kidney disease). These KCL research studies have had a significant impact by making a major contribution to national and international clinical guidelines, including UK NICE guidelines and the 2012 National Kidney Foundation KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease.
Impact: Health and wellbeing; translation of a clear evidence base for reducing red blood cell use in intensive care and surgery into guidelines and changed clinical practice.
Significance: A 20% reduction in overall UK red blood cell usage between 2002-2012, saving the NHS approximately £100M annually; 7000 fewer patients are exposed to red cell transfusion annually, saving 500 lives.
Beneficiaries: Patients in intensive care units; the NHS and healthcare delivery agencies.
Attribution: Studies were led by Walsh at UoE with NHS and Canadian collaborators.
Reach: 7000 patients per year, UK-wide; incorporation into international guidelines.
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.
Professor Platt and colleagues at the University of Oxford have developed the drug miglustat, the first oral therapy for rare lysosomal storage diseases. These are primarily neurodegenerative diseases that affect 1 in 5,000 live births, always leading to premature death. In 2009, miglustat became the first treatment to be licensed for treating neurological manifestations in Niemann-Pick disease type C (NPC). It is now prescribed for the majority of NPC patients worldwide, and has led to significant improvements in both life expectancy and quality of life. Miglustat was approved for type 1 Gaucher disease in 2002 and, since 2008, has proved an effective treatment for patients previously stabilised with enzyme replacement therapy; miglustat has the additional benefit of improving bone disease. Sales of miglustat since 2008 have generated CHF 315 million in revenues for Actelion, the company sublicensed to sell the drug.
Novel work undertaken at this centre has demonstrated that vitamin B2 (riboflavin) can significantly decrease BP, specifically in people with a common genetic variant affecting the folate-metabolising enzyme MTHFR. The extent of BP-lowering demonstrated is as good as that expected from BP-lowering drugs and much better than that found with common dietary approaches and furthermore, the effect is independent of concurrent BP-lowering drugs. These findings offer a simple, cost-effective targeted treatment for the management of BP in this genetically at-risk group. The global prevalence of this genetic variant is 10% but can be as high as 32% in other countries such as Mexico and Northern China.
Research led by University of Oxford scientists has resulted in widespread use of the humanised therapeutic antibody, Campath (alemtuzumab), in patients with chronic lymphocytic leukaemia (CLL). Licensed by both the European and American regulatory authorities in 2004 for the treatment of CLL, Campath is used as first-line treatment for patients with aggressive forms of the disease and following relapse. It can induce long-term clinical remission even in cases resistant to other drugs. Campath has now been used in approximately 15,000 patients, and has generated revenues of approximately £750 million from the licensed treatment of CLL.
Myeloproliferative neoplasms (MPN) are a group of blood disorders that affect more than 9,000 people in the UK every year. King's College London (KCL) research on the biology, diagnosis and treatment of MPN has had the following significant impacts:
Research led by Professor Brown has led to widespread changes in clinical practice regarding the management of Hypertension. Following his demonstration that patients' response to drugs for Hypertension is variable (in a systematic manner), subsequent clinical guidelines acknowledged the variability among patients, and changed from recommending the same treatment for all patients, to an algorithm based on the Cambridge AB/CD rule. The simplicity of the AB/CD rule led to popularity among doctors, and adoption by national bodies — British Hypertension Society, NICE, and foreign guidelines, and by textbooks of Medicine. The guidelines arising from his research have contributed to improved health outcomes in the UK. Specifically, NICE's simple and rational guidance how to reach strict targets for blood pressure is credited with changing the UK from the poorest to best performing country in Europe.
Research on clinically important red blood cell membrane proteins has helped avoid unnecessary treatment of Rhesus negative pregnant women and enabled the early diagnosis of a rare kidney disease. During the late 1990s, researchers at the University of Bristol, in collaboration with the Blood Service in Bristol, cloned, sequenced and characterised many red blood cell membrane proteins important for transfusion, including the Rhesus proteins and Band 3/AE1 (SLC4AE1 gene). The work on Rhesus proteins facilitated the use of less invasive genetic screening methods to ascertain whether treatment was required to avoid Haemolytic Disease of the Foetus or Newborn (HDFN). In the UK, 5,000 women have been screened since 2001. Within the first six months of implementation of a Danish national screening program in January 2010, 862 women avoided unnecessary treatment. Reducing unnecessary treatment of mothers has saved resources and avoided unnecessary exposure to human derived blood products. In addition, research that has identified specific SLC4AE1 gene mutations that cause the rare kidney disease called distal renal tubular acidosis has enabled the early diagnosis and treatment of the disease, resulting in improved outcomes for patients.