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Eliminating Death from Heart Failure in Thalassaemia Major Using T2* Cardiovascular Magnetic Resonance

Summary of the impact

The development of a cardiac magnetic resonance technique at Imperial College and Royal Brompton Hospital to quantify myocardial iron concentration has resulted in the early identification of thalassaemia major patients at risk of heart failure and targeted cardiac treatment with a hitherto little used iron chelator, deferiprone, following randomised controlled trials of efficacy. Since 2008 these advances have resulted in a 71% reduction in cardiac death from myocardial siderosis in thalassemia major in the UK.

Submitting Institution

Imperial College London

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences

New treatment and treatment monitoring for iron overload in thalassaemia patients

Summary of the impact

The iron and red cell disorders group at UCL has worked for over 20 years on the pathophysiology of transfusion-dependent iron overload in thalassaemia patients, using models of iron uptake and overload and translating these into clinical practice. In collaboration with Novartis, a new treatment, deferasirox, was developed, which is now the treatment of choice for iron overload in the western world. In addition, a method for monitoring iron overload in the heart was developed in collaboration with Dr Pennell at the Brompton and pioneered in patients at UCL Hospital (UCLH) and the Whittington Hospital. This has become the standard approach worldwide.

Submitting Institution

University College London

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences, Pharmacology and Pharmaceutical Sciences

LiDCO: Minimally invasive measurements of cardiac output and haemodynamics by lithium dilution and pulse contour analysis

Summary of the impact

Researchers at King's College London developed an algorithm for a novel method of pulse contour analysis that allows continuous estimation of key haemodynamic parameters from an arterial line (PulseCO). They also invented a novel method for clinical measurement of cardiac output using lithium as an indicator and lithium-sensitive ion selective electrodes (LiDCO). Together, these allow rapid and minimally invasive measurements of haemodynamics and fluid status in high risk patients undergoing surgery or in an intensive care unit, facilitating goal directed therapy and reducing complications and costs. LiDCO and PulseCO form the key underpinning technologies for the clinical monitoring systems produced by LiDCO PLC, an AIM listed company with an international customer base.

Submitting Institution

King's College London

Unit of Assessment

Biological Sciences

Summary Impact Type

Technological

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences, Medical Physiology

Improving the health and performance of distance runners

Summary of the impact

The research outlined below concerning medico-physiological issues in distance runners has directly informed medical policy, investigations and therapy strategies applied to elite distance runners, and raised the profile of issues relating to the Female Athlete Triad for coaches such as those within British Athletics and England Athletics.

The research findings have been disseminated via several avenues, such as the education of Sport and Exercise Medicine (SEM) doctors (through content for lectures delivered on SEM programmes at bachelors and masters level), and via CPD workshops for coaches and SEM practitioners, thus with the capacity to directly affect medical practice.

Submitting Institution

St Mary's University, Twickenham

Unit of Assessment

Sport and Exercise Sciences, Leisure and Tourism

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Public Health and Health Services

1. Evidence based management strategies for Heritage iron

Summary of the impact

Most museums in Britain contain collections of archaeological and heritage iron objects that are rapidly rusting away due to an absence of evidence-based management strategies for their display and storage. Research at Cardiff University has identified the corrosion mechanisms driving the destruction of this iron and, through experiment, has quantified the effectiveness of desiccation and chloride desalination treatments either to prevent or slow its corrosion. The research has led to the development of clear guidance for devising, implementing and managing preservation strategies for iron. These have been adopted by English Heritage, the British Museum and other institutions. The guidelines underpin an imaginative use of desiccation to preserve Brunel's iron ship ss Great Britain as an international heritage attraction, centre for research and academic study of Brunel and a significant contributor to local and national economies.

Submitting Institution

Cardiff University

Unit of Assessment

Geography, Environmental Studies and Archaeology

Summary Impact Type

Cultural

Research Subject Area(s)

Chemical Sciences: Analytical Chemistry, Other Chemical Sciences
Engineering: Materials Engineering

Developing drugs targeting neuroregeneration in stroke

Summary of the impact

Neurons in the central nervous system do not normally regenerate following injury, due in part to the presence of `inhibitory' molecules that actively prevent the growth and/or collateral sprouting of axons. King's College London scientists identified myelin associated glycoprotein (MAG) as the first myelin inhibitory molecule and demonstrated that inhibition of MAG function with a monoclonal antibody promotes axonal regeneration. They have gone on to promote MAG and its receptor (called the NgR1) as druggable therapeutic targets. Their discovery has led the UK's largest pharmaceutical company — GlaxoSmithKline — to develop monoclonal antibodies to MAG and a second myelin inhibitor as clinical drug candidates. The anti-MAG therapeutic successfully completed Phase I and II clinical trials in humans for stroke during 2008-2013.

Submitting Institution

King's College London

Unit of Assessment

Biological Sciences

Summary Impact Type

Technological

Research Subject Area(s)

Biological Sciences: Biochemistry and Cell Biology
Medical and Health Sciences: Neurosciences, Pharmacology and Pharmaceutical Sciences

Better treatment of anaemia and improved quality of life in patients with chronic kidney disease

Summary of the impact

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.

Submitting Institution

King's College London

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Biological Sciences: Biochemistry and Cell Biology
Medical and Health Sciences: Clinical Sciences

Establishment of CoCo Therapeutics to take forward new drugs for Alzheimer’s disease

Summary of the impact

Alzheimer's disease (AD) presents society with one of its biggest challenges, yet despite the investment of billions of dollars there are only two classes of drug approved that have minimal benefit in patients. Scientists at King's College London have implicated dysregulation of retinoid signalling as an early feature of the disease and identified the retinoic acid receptor (RAR) family as an attractive drug target. They have gone on to design and patent protect novel orally available RARα selective agonists and demonstrated that they have the potential to restore many of the deficits reported in AD patients. Advent Venture Partners has provided funds to establish a new UK biotechnology company, CoCo Therapeutics Ltd, in partnership with the Wellcome Trust and KCL, to progress this KCL research into the development of a new treatment for AD.

Submitting Institution

King's College London

Unit of Assessment

Biological Sciences

Summary Impact Type

Technological

Research Subject Area(s)

Biological Sciences: Biochemistry and Cell Biology
Medical and Health Sciences: Neurosciences

The development of a “first-in-class” N-cadherin antagonist for cancer

Summary of the impact

The cell adhesion molecule N-cadherin has been shown to be required for the survival of cancer cells, their metastasis and the formation of new blood vessels in solid tumours, however, cell adhesion molecules like N-cadherin were generally not considered to be "druggable." Scientists at King's College London have contributed to the development of a "peptide-pipeline" of novel N-cadherin antagonists, including the cyclic HAV peptide (N-Ac-CHAVC-NH2), also now known as Exherin and/or ADH-1, as a "first-in-class" N-cadherin antagonist. This compound was granted FDA organ drug designation for Melanoma in 2008 and successfully completed a number of phase I and II clinical trials, with an additional clinical trial currently recruiting. The demonstration that N-cadherin peptides can be used to treat cancer has changed the perception of what is possible and opened up new clinical and commercial opportunities.

Submitting Institution

King's College London

Unit of Assessment

Biological Sciences

Summary Impact Type

Technological

Research Subject Area(s)

Biological Sciences: Biochemistry and Cell Biology

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