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Research at the University of Nottingham has defined the clinical phenotype and management of lymphangioleiomyomatosis, a rare and often fatal multisystem disease affecting 1 in 200,000 women worldwide. The group has led the development and evaluation of new therapies and diagnostic strategies which are now part of routine clinical care. The research has underpinned the transformation of this previously under recognised and untreatable disease into a condition recognised by respiratory physicians, with international clinical guidelines, patient registries, clinical trials, specific treatments and a UK specialist clinical service.
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.
Meningococcal meningitis is a life-threatening acute disease affecting 1.2 million people every year. Accurate and rapid diagnosis is essential for optimal patient response; however, bacterial culture tests are slow and undermined by the immediate administration of antibiotics, resulting in sterile cultures.
The Surrey team developed a rapid, non-culture-based diagnostic test for meningitis and septicaemia: this test is now routinely used for diagnosis of meningococcal disease worldwide, and was also instrumental in the implementation and monitoring of control measures for the disease, such as life-saving vaccination campaigns. Together these have contributed to the halving of adult mortality rates from meningitis worldwide.
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.
Studies conducted at Imperial College, over the last 20 years, have improved the rational, evidence-based treatment of schizophrenia. Our research has covered symptomatology, neurocognitive function, medication side effects, and comorbid substance use, and involved clinical trials of pharmacological and psychosocial treatments. We lead national quality improvement programmes supporting the implementation of psychopharmacological practice standards. Our work has impacted upon the understanding, clinical assessment and treatment of this condition in both first-episode patients and established schizophrenia, and has improved prescribing practice and the identification and assessment of side-effects.
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.
The Boutelle team has developed a biosensor that uses rapid-sampling microdialysis (rsMD) to detect ischaemia (restricted blood supply to tissue) during surgery and intensive care. The rsMD biosensor is implanted into tissue at risk and provides a real-time readout of chemical markers of metabolism. By 2009, technical improvements researched in the Department of Bioengineering had made the system suitable for routine clinical use. The system has reduced morbidity and mortality by alerting the surgical team to otherwise undetected ischaemia. It has been used by an international consortium of clinical centres to help decide treatment in approximately 100 patients with brain injury. More recently it was adopted by a Portsmouth hospital to monitor cancer patients undergoing reconstruction of the face and jaw; the biosensor detected a failure of perfusion in transplanted tissue in two of the first ten patients, prompting the surgical team to remove otherwise undetected blood clots that could have led to death from septicaemia.
The UCL Centre for Amyloidosis and Acute Phase Proteins conducts world-leading research and development that has rapidly fed through to patient care. These include advances in the diagnosis of amyloidosis and clinical characterisation of many new subtypes including genetic forms, development and application of new biomarkers to monitor disease activity and progress, new modalities of imaging and better treatment. The consequences have been new standards of clinical care adopted nationally and internationally, improved and more accurate diagnosis, steady improvements in the outcomes of this disease, major investment by the NHS and adoption of new clinical metrics by the pharmaceutical industry to enable research on specific new therapies currently in development.
Neuroblastoma is a paediatric cancer that arises from the sympathetic nervous system. The average age at diagnosis is 18 months and the disease accounts for approximately 15% of all childhood cancer-related deaths. Determining optimal treatment for individual patients is crucial for increasing chances of survival and for reducing side effects of chemotherapy and radiotherapy. Newcastle-led research identified unbalanced 17q gain as the most common segmental chromosomal abnormality (SCA) in patients with neuroblastoma; this was present in more than 50% of patients. Gain of 17q is now one of the key SCAs used to determine treatment for patients in a European neuroblastoma trial and in UK treatment centres. Newcastle research also led to the development of a simple diagnostic test for the detection of the main SCAs in neuroblastoma.
Psoriatic arthritis (PsA) is a chronic inflammatory disease of joints, skin and tendons that affects 0.5-0.8% of the population worldwide. PsA can cause substantial psychological and social problems and also causes increased risk of death from cardiovascular disease. Research conducted by Prof Iain McInnes at the University of Glasgow in partnership with leading pharmaceutical company, Janssen, has provided robust evidence of the clinical benefits and safety of the cytokine blocker ustekinumab, leading to its approval for use for PsA by the European Medicines Agency in July 2013. This was the first approval of a PsA drug with a new mode of action in a decade, providing a novel treatment for approximately 1.25 million PsA patients across Europe.