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Essential thrombocythemia (ET) is a pre-leukaemic chronic myeloproliferative neoplasm (MPN) the management of which had been hampered by a lack of prospective randomised studies. Professor Green (University of Cambridge Department of Haematology) was Chief Investigator for the MRC primary thrombocythemia-1 (PT-1) study, initiated in 1997, which compared hydroxyurea plus aspirin with anagrelide plus aspirin in patients with ET at high risk of thrombosis. This clinical trial remains the world's largest randomised study of any MPN and its results demonstrated that hydroxyurea plus aspirin should be first line therapy, a result embedded in current guidelines. This outcome had a major effect on the world-wide use of anagrelide for patients with ET and is estimated to have saved the NHS over £22M per year in drug costs since the results of the trial were published in the NEJM.
Diagnostic tests have been successfully developed for identification of the cause of erythrocytosis, particularly in patients with unexplained forms of this rare disease. A diagnostic service with worldwide reach was developed for the genetic characterisation of patients that carry mutations identified by the Queens's group. It deals with approximately 100 samples per year referred for investigation for this rare disease from the UK, Europe and further afield. Proper diagnosis helps in management of patients with erythrocytosis where the problem is not mutation in one of the familiar causative genes. A pan-European web-based database has been established to collect information on long-term outcomes to inform patient management.
Individuals with Xeroderma pigmentosum (XP) are extremely susceptible to sunlight-induced skin cancers and, in some cases, develop neurological problems. Alan Lehmann has developed a cellular diagnostic test for this disorder. This test is now conducted as an integral part of a multi-disciplinary XP specialist clinic in London, which was established as a direct result of Alan Lehmann's research in Sussex and which has led to the improved diagnosis and management of the disorder and an improved quality of life for affected individuals.
Ataxia telangiectasia (A-T) is an inherited disease affecting multiple systems in the body, causing severe disability and death. Work led by Professor Malcolm Taylor at the University of Birmingham has been central to the biological and clinical understanding of this disease, from the identification of the gene responsible to the clarification of related conditions with different underlying causes. As a result of this work, within the 2008-13 period, his laboratory has been designated the national laboratory for clinical diagnosis of A-T — a service also offered internationally — and has also changed national screening policy for breast cancer, following his confirmation of the increased risks of A-T patients and those who carry a single copy of the gene for this type of tumour. Furthermore, he has contributed in a major way to patient support for this condition.
Sudden cardiac death causes 4.5 million deaths worldwide each year many of which could be prevented by implantable cardioverter defibrillators (ICDs), but these also carry risks. Research in the groups of Huang and Grace has led to diagnostic assays offering three times the predictive accuracy of current approaches in guiding cardiologists concerning indications for ICD implantation. The assay has been clinically trialled; since 2008, through the trial, the lives of three patients identified by the assay as at high risk were saved. Further work led by Grace and colleagues provided an improved, subcutaneous ICD (SICD); Grace also participated in a US-based clinical trial (NCT00399217) providing the evidence required for FDA approval supporting also later inclusion into NICE guidance. Since 2008 the SICD has been implanted in over 2500 patients in 16 countries.
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.
Research conducted at UCL/UCLH over the last 20 years has enabled the identification of adults with acute leukaemia who are most likely to benefit from the use of stem cell transplantation, i.e. those with acute leukaemia in first remission. The treatment is highly intensive, potentially toxic and expensive high-dose chemotherapy followed by haemopoietic stem cell transplantation, and is inappropriate for some patients. The work has made a major contribution to the development of guidelines worldwide for the treatment of this disease. Improved patient selection for transplantation results in improved survival, less toxicity with improved overall quality of life, and a more appropriate use of NHS resources.
This case study outlines the impact of novel omega-3 fatty acid therapy for sickle cell disease on health and policy. 128 patients on the treatment since 2010, and another 300 who started to receive it in June 2012 have seen remarkable improvements in health and quality of life as assessed by reductions in hospital admission and absence from work/school due to the disease. A panel of experts set up by the Ministry of Health of Sudan to evaluate the evidence recommended the integration of the therapy in the management of the disease in a policy report dated December 20, 2012. The Ministry has accepted the recommendation.
The work of Colledge and colleagues between 2000 and 2007 has identified and characterised a molecule which is an important regulator of fertility: the neuropeptide kisspeptin.
The identification of its role in fertility has led to kisspeptin and its analogues being tested in clinical trials to make IVF treatment safer (Phase II: one trial), and as therapeutic agents for reproductive system conditions such as delayed puberty, menopause and absence of menstruation (Phase I: four trials). In April 2013, 11 months after the start of the Phase II IVF study, a healthy baby has been born to a participant treated with kisspeptin. Patients enrolled in these fertility trials have testified to the improvement in quality of life which the hope of being able to conceive that this alternative to conventional IVF has brought them.
Basic molecular genetic research undertaken over the last 20 years by UCL Cardiovascular Genetics has had a significant impact on the identification and treatment of patients with familial hypercholesterolaemia (FH). We have developed DNA testing methods in the three genes currently known to cause FH and have established DNA diagnostic protocols which are now in wide use throughout the UK. As a direct consequence of our work, we estimate that up to 3,000 FH patients in the UK have had their diagnosis of FH confirmed by a DNA test. Our work led to the National Institute of Health and Clinical Excellence (NICE) in 2008 strongly recommending DNA and cascade testing and early treatment with high intensity statins, and furthermore, the inclusion of FH checks in the NHS's Vascular Checks programme.