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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.
Researchers from the University of Oxford identified the novel human protein Forkhead box transcription factor 1 (FOXP1) and showed it to be an important prognostic biomarker in cancer. Expression of FOXP1 can distinguish those patients with diffuse large B-cell lymphoma (DLBCL) who are at high risk of disease progression, making it possible for clinicians to target more intensive therapy to this group. DLBCL accounts for one third of lymphomas and is the seventh commonest form of cancer. The anti-FOXP1 monoclonal antibody developed by Oxford University is now used worldwide in clinical diagnostics.
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.
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.
Sumbayev and colleagues have shown that gold nanoparticles represent an excellent platform for the specific delivery of drugs, targeting the HIF-1 biochemical pathway as a novel therapeutic target for diseases such as allergy, leukaemia and other autoimmune disorders. Two international, non-academic institutions have altered the direction of their work as a result of this research and two SMEs have revised their operational procedures and invested in the applied research that derives from this work.
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.
Pioneering research in miniature in-vitro microfluidic diagnostic systems at the University of Southampton has produced major economic impacts by driving new business activities in major multinational corporations. Philips Research Cambridge are investing £5 million p.a. and employing 12 FTEs to develop new Point of Care systems for rapid diagnosis and management of disease based on the research. Patented advances in electronic fluid-handling technologies is driving £3 million R&D investment in Sharp Labs Europe in partnership with Southampton to develop a rapid assay platform for prompt detection of antibiotic-resistant bacterial infections. Health impacts from the research are the provision of new home based diagnostics that provide targeted and early risk identification resulting in improved patient healthcare and reduced costs.
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.
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.
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.