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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.
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.
Malaria is endemic in more than 100 countries but its rapid and accurate diagnosis in locations remote from clinical laboratory facilities remains challenging yet desperately needed. This case study describes how scientific discoveries made in the field of digital data storage have been developed and applied to deliver a rapid, reliable and low cost malaria diagnosis sensor suitable for field application. Diagnostic devices have been both laboratory-tested and clinically trialled on over 900 patients under adverse field conditions in malaria endemic countries with very promising results. The health impact includes not only significantly reducing unnecessary treatments but potentially saving millions of lives.
Research at the UCL School of Pharmacy has positively influenced healthcare in startle disease/hyperekplexia, a rare disease that affects humans and several animal species, including dogs, horses and cattle. The identification and functional characterisation of mutations in genes involved in human startle disease by researchers at the School has improved genetic diagnostics and patient care. Our research on startle disease in cattle and dogs has also led to new non- invasive diagnostic tests that have alleviated animal suffering and reduced negative economic impacts on farmers. Overall, our findings have been translated into tangible benefits for the human and animal populations affected by this disease and have changed the way in which the disease is diagnosed and treated. We have also significantly increased the awareness of this rare disorder by communicating with academics, healthcare and veterinary professionals, and the general public.
A long programme of research By Neil Avent has led to the development of powerful screening and diagnostic measures. It has enabled the implementation of molecular blood grouping and Non- invasive prenatal diagnosis (NIPD) into clinical use. The work began with research that took the lead in developing the commercially available products BLOODchip and MLPA, used extensively in the management of difficult to transfuse patients. This was developed into investigations of NIPD of fetal blood groups (particularly RhD), and through EC funding, drove workshops to establish non-invasive RhD typing as routine in the clinical management of haemolytic disease of the fetus and newborn. This work has shaped the standardisation of NIPT for fetal Rhesus D (RhD) and fetal sexing via External Quality Assessment (EQA) and the EC network Eurogentest.
Research by the University of Southampton has helped transform the understanding and treatment of chronic lymphocytic leukaemia (CLL), the most common leukaemia, affecting around 2,400 patients each year in the UK and 17,000 in the USA. Southampton's widely cited studies revealing the existence of two subsets of CLL have been crucial in giving clinicians and patients in the UK and overseas a much clearer indication of the likely disease course. The predictive information is now included in all clinical trials and in international guidelines, delivering greatly improved care. The research has also inspired the development of a new drug given "breakthrough" status by the Food and Drug Administration in the United States.
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.
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.
Impact: Changed public health policy by quantifying the level of asymptomatic vCJD infection in the population and the mechanism of its transmission, and by identifying cases of human-human transmission of vCJD via blood products.
Significance: UoE work informed the public and policy-makers of the risk of vCJD transmission, which resulted in policy changes and the implementation of precautions to prevent vCJD transmission and to limit the chance of a self-sustaining blood- or tissue-contamination-related secondary epidemic.
Beneficiaries: Patients, the NHS and healthcare delivery organisations, government, policy-makers.
Attribution: The work was carried out at UoE in the National Creutzfeldt-Jakob Disease Research and Surveillance Unit (NCJDRSU) and the Roslin Institute UoE (Roslin) with UK collaborators.
Reach: International, particularly UK and North America.
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.