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John Williams and colleagues found that serum homocysteine predicted cognitive decline and predicted the potential for vitamin B12 in treatment of dementia, including Alzheimer's Disease. This finding has led to the production of 2 novel cobalamin compounds, glutathionyl cobalamin (GSCbl) and N-acetyl cysteinyl cobalamin (NACCbl), in collaboration with Kent State University (USA), the use of which were patented in USA. We have also identified a novel anti-oxidant activity of vitamin B12. This work has led to the production of Betrinac sold by the Chester company, Cobalz Ltd, in the UK and PamLab Llc, USA.
Dementia is one of the greatest problems facing society today, both in financial terms and in terms of the quality of life of patients and caregivers. Newcastle research identified that cholinesterase inhibitors (CHEIs), originally licenced for use in Alzheimer's disease, would be of greater benefit in two other types of dementia; Lewy body dementia and Parkinson's disease. CHEIs are now recommended in national and international guidelines as a treatment for the cognitive and psychiatric symptoms associated with both of these conditions, which previously had no effective treatment. CHEIs are also licenced worldwide for use in Parkinson's dementia, and are used off- licence across the world as a first-line treatment for dementia with Lewy bodies.
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.
Research by a team at Southampton into amyloid beta protein (A03b2) immunisation to treat Alzheimer's disease has been key to changing the way the global medical community understands and reacts to the disease. The first to observe that A03b2 immunisation clears A03b2 plaques, the team's studies were pivotal in initiating and informing the safe clinical trial development of 40 immunotherapy agents; investments of $3bn by the pharmaceutical industry; and 30 phase II and phase III studies. The research shaped US government policy on new safety measures for clinical trials and played a leading role in the doubling of UK funding to tackle Alzheimer's.
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.
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.
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.
The Brain, Performance and Nutrition Research Centre (BPNRC) has an international reputation for research conducted in collaboration with industry to assess the impact of nutrition and dietary interventions on brain function. Our research benefits our industrial partners financially, in terms of increased product sales, and by providing evidence supporting the introduction of new products that improve consumer wellbeing. This case study focuses on research that supported Bayer to develop successful brands with public health benefits.
Newcastle research on dementia contributed two aspects that helped to shape high-level policy: first that prevalence of the condition was higher than previously suspected, with implications for care of the ageing UK population. Secondly, that patients often experienced long delays before a diagnosis of dementia was given, leading to distress both for patients and their families. This research informed policy documents such as the Prime Minister's 2012 Challenge on dementia and national guidance in the form of commissioning packs. Patients benefit from more timely diagnosis with a better understanding of their needs and wishes and the NHS benefits through potential reductions in long term care costs.
Cognitive Stimulation Therapy (CST) is an evidence-based, brief, group therapy for people with mild to moderate dementia. It was developed and evaluated by UCL in collaboration with Bangor University. Our research showed significant benefits in cognition and quality of life plus cost-effectiveness. Cognitive Stimulation for people with mild/moderate dementia of all types is recommended by NICE and is now in widespread use across the UK and the rest of the world in a variety of settings including care homes, hospitals and the community. A recent audit by the Memory Services National Accreditation Programme reported that 66% of UK memory clinics surveyed were using CST.