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Dementia with Lewy bodies (DLB) is one of the most common subtypes of dementia. Although DLB shares characteristics with Alzheimer's disease, the condition requires specific treatment and care. New diagnostic criteria generated at Newcastle allow diagnosis of DLB as a distinct condition from Alzheimer's, and these criteria have been incorporated into five national and international guidelines. The work also resulted in an accurate and sensitive diagnostic technique, commercialised by GE Healthcare as the DaTSCAN imaging tool, which is approved by the US Food and Drug Administration and the European Medicines Agency. These new diagnostic criteria allow appropriate treatment and management of DLB for the first time.
Research at UCL has greatly contributed to the understanding of the dopaminergic system in Dementia with Lewy bodies (DLB) with an initial publication in Lancet 1999 showing that patients with DLB have reduced uptake of dopamine transporter compared to patients with Alzheimer's disease and that this could be a useful biomarker for DLB. Since then the research conducted on imaging of dopamine transporter uptake has had national and international impact and significantly contributed to a change made in the Revised Clinical Criteria for the diagnosis of Dementia with Lewy bodies (McKeith et al 2005) which now includes "low dopamine transporter uptake in the basal ganglia demonstrated by SPECT imaging" as a "suggestive feature" for DLB.
Atopic eczema is a disabling long-term skin condition affecting ~2% of the UK adult population. The mainstay of treatment remains topical steroids and moisturisers, but many adult patients with atopic eczema have resistant disease that can significantly impair quality of life. Newcastle University researchers conducted clinical trials that showed both whole-body ultraviolet B phototherapy and systemic (tablet) treatment with the immunosuppressant drug azathioprine were effective treatments for adults with atopic eczema resistant to standard topical treatments. UK and European guidelines written after 2008 recommend UVB phototherapy and azathioprine for atopic eczema, and survey data indicate that both are now widely used to treat the disease in the UK.
Congenital myasthenic syndromes (CMS) are inherited neuromuscular disorders caused by defects at neuromuscular junctions, which are often a result of acetylcholine receptor gene mutations. A subset of CMS patients (around 14% in the US and Europe) have limb-girdle myasthenia (LGM). This disease can be highly disabling with symptoms including increasing weakness of skeletal muscles. As a result of collaborative work between Newcastle and Oxford, it was determined that many LGM patients have a mutation of the Dok-7 gene (unrelated to the acetylholine receptor), and do not, therefore, respond to standard CMS treatments. Since then, a number of additional mutations have been discovered, and genetic testing is now available for the majority of known LGM-causative genes. Crucially, Dok-7 patients, and those with other non-receptor related mutations, can now be diagnosed accurately and treated effectively, with ephedrine and salbutamol (in the US, albuterol). This significantly improves these patients' quality of life by enabling them to walk and breathe unassisted.
Malignant pleural mesothelioma (MPM) is a treatable but incurable cancer that originates in the cells lining the lungs. Over 14,000 people worldwide are diagnosed annually with MPM. Antifolates are often used in cancer therapy, but side effects are a major issue. A retrospective analysis of cancer trials and phase 1 trial of MPM patients, carried out by Newcastle in collaboration with Eli Lilly Pharmaceuticals, determined that plasma homocysteine levels were a good predictor of drug toxicity in cancer patients treated with the antifolate pemetrexed, and that this drug was well tolerated by patients with low homocysteine levels. It was also determined that pemetrexed treatment should be supplemented with vitamin B12 as well as folic acid, to reduce drug toxicity. Ultimately, this permitted the continued development of pemetrexed, which otherwise would have been too toxic for clinical use. It is now the only licensed drug for MPM treatment in combination with platinum-based chemotherapy.
Research carried out by Professor David Smith of the University of Oxford established that B vitamins could slow the rate of Alzheimer-related brain atrophy and cognitive decline in people with mild cognitive impairment (MCI), an early stage of Alzheimer's disease which is common in the elderly. Since 2008 the impact on sales and marketing of B vitamins worldwide has been significant; [text removed for publication], and over-the-counter and prescription B vitamin products marketed as helping to maintain memory function have achieved sales worth many millions of US dollars. Some doctors now prescribe B vitamins for the group of MCI patients identified by Smith as being most at risk.
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.
Warfarin is an anti-coagulant drug prescribed to tens of millions of people in the UK and US who are at high risk of developing blood clots. Because individual sensitivity to warfarin varies in the population there is a risk of overdosing the drug and causing serious bleeding and even stroke in many people when starting treatment. In 1999 researchers at Newcastle University were the first to demonstrate a statistically significant link between a person's genotype and the appropriate dose of warfarin. In 2010 the US Food and Drug Administration (FDA) mandated inclusion of a table of dose recommendations based on genotype in the warfarin prescribing information leaflet accompanying the drug. Newcastle research forms the basis of the 2009 international standard algorithm for gene-guided dosing of warfarin. This approach has been adopted by large US medical centres and the FDA states that it will prevent 17,000 strokes a year in the US.
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.
CANTAB-Paired Associates Learning (PAL) was developed to detect early memory problems in Alzheimer's disease; and was recently (in 2012) launched by Cambridge Cognition (floated on the London Stock Exchange in April 2013) as a mobile (iPad) application (CANTABmobile™) suitable for use in GP clinics. This and other cognitive tests from the CANTAB battery have also been employed in 77 clinical trials since 2008, involving hundreds of sites world-wide, by most of the major pharmaceutical companies and by biotech, device and nutraceutical companies. CANTABmobile™ currently has 166 licensed user-practitioners including six clinical commissioning groups implementing the national initiative for early diagnosis.