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Alzheimer's disease (AD) affects one in seven of the population over 60 years of age, and represents an increasing burden on worldwide medical and care resources. Treatments currently available are symptomatic. Despite pharmaceutical industry efforts there has been little indication of a marketable product for long-term treatment.
To address this problem, a joint venture was established in 2001 between the University of Aberdeen and TauRx Pharmaceuticals. A team was created of chemists, biologists, animal behaviourists, working together with a clinical trial team. A drug effective against the progress of AD based on the compound methylene blue was synthesised and scaled up within the Chemistry Department (led by Professor John Storey), with a quality that was proved acceptable through successful phase two clinical trials (2006-8), and is now used in phase three clinical trials which are due to complete in 2015. Several other drug candidates have also been developed and evaluated in pre-clinical and phase one clinical studies that show promise. Collaborations with commercial pharmaceutical companies have as a result led to the manufacture of significant quantities of drug medicines for TauRx Pharmaceuticals based on IP generated within the Chemistry Department and these drugs have been used in clinical trials and for named patient supply (c. 60 patients). This has resulted in increased commercial revenue for these companies and the creation of new employment.
The drug galantamine (Reminyl) received approval for the treatment of early stages of Alzheimer's disease in 2001. However it was not made available on the NHS until March 2011, the effective onset date for the impact. The decision as to whether a treatment is available on the NHS is made by the National Institute of Health and Care Excellence (NICE), who sought additional clinical data and a rationale for the action of the drug. The mechanism of action was elucidated by Lancaster researchers that included chemists and biomedical scientists. These results were part of Alzheimer's Society's campaign to convince NICE to make the drug available on the NHS for early stage Alzheimer's. The resulting impact was direct, enhancing the quality of life for 100,000s of Alzheimer's patients (318,000 galantamine prescriptions were dispensed in the UK in 2012 [8]), with indirect impact on spouses, immediate family, and carers. The impact continues as new patients come into the pool.
The UCL Centre for Amyloidosis and Acute Phase Proteins has designed and developed new chemical entities targeting serum amyloid P component (SAP), C-reactive protein (CRP) and transthyretin, for novel therapeutic approaches to amyloidosis, Alzheimer's disease, cardiovascular and inflammatory diseases. The UCL spin out company, Pentraxin Therapeutics Ltd, founded by Sir Mark Pepys to hold his intellectual property (IP), has licensed two programmes to GlaxoSmithKline (GSK). These highly synergistic, collaborative multi-million pound developments, strikingly exemplify new working relationships between academia and the pharmaceutical industry.
The University of Aberdeen's discovery of a novel drug for the treatment of rheumatoid arthritis and related inflammatory/autoimmune disorders has brought substantial industrial investment in research and development. The new drug is expected to enter clinical trials shortly and has the potential to transform the way rheumatoid arthritis is currently treated, as few patients currently have access to the expensive biological agents which dominate existing therapy. Aberdeen has commercialised its research into a university spin-out company and subsequently licensed the programme to a UK drug-development company, Modern Biosciences plc. The research has created and protected UK expertise and jobs.
The specific impacts on commerce have been: substantial industrial investment in research and development, job creation and protection within UK industry, commercialisation of a new product via a licencing deal, and academic consultancy in industry.
Galantamine (Reminyl®) is one of the drugs recommended by NICE for treatment of Alzheimer's disease (AD). Until recently, it was approved only for the moderate stage of AD. In 2011, NICE guidance was changed to recommend that this drug could also be prescribed for early-stage AD. This has had a major impact on the lives of AD sufferers. In published research arising from an Alzheimer's Society Project Grant, Prof. Allsop at Lancaster demonstrated that Galantamine inhibits Aβ aggregation and so should be prescribed as early as possible during the course of AD due to its potential disease-modifying properties. This research underpinned arguments made by the Alzheimer's Society who were one of the key players in pressing for the change in NICE recommendations.
Miltefosine is the first oral drug to be developed for the treatment of leishmaniasis, a worldwide parasitic infection with up to 12m cases. Also developed as a cancer drug, miltefosine was identified and tested for leishmaniasis therapy at LSHTM and has been added to WHO's essential medicines list as a result of subsequent clinical trials. It has been widely used for the treatment of visceral leishmaniasis (VL) in India, Nepal and Bangladesh, and for the cutaneous form of the disease in Latin America. Phase III and IV clinical trials of combination therapies including miltefosine have been carried out in India.
A new anti-inflammatory molecule FX125L was developed by David Fox at Warwick, in collaboration with David Grainger (Department of Medicine, Cambridge) and Funxional Therapeutics Ltd (FXT). Research in lead optimization, mechanistic preclinical chemistry, synthetic route development (for scale-up), and CMC (chemistry, manufacturing and controls) was conducted at Warwick. As a result FX125L completed Phase 1 and entered Phase 2 clinical trials in humans for the treatment of asthma or other inflammatory diseases. Its sale to Boehringer Ingelheim generated a multi-million pound return for FXT and its investors.
Labelled compounds form an essential part of drug discovery and development within the pharmaceutical industry. Novel iridium catalysts, developed by Kerr at WestCHEM since 2008, have introduced a step-change in the ability to label pharmaceutical candidate compounds with radioactive (tritium) or non-radioactive (deuterium) isotopes.
The catalysts are applicable to specific types of compounds that comprise approximately one-third of all drug candidates. Advantages of the catalysts include greater efficacy (less catalyst needed and higher yield of labelled product, giving cost savings), greater speed (efficiency savings), and a significant decrease in radioactive waste compared with previous methods (environmental and safety benefits).
Even since 2008, their adoption within the pharmaceutical industry has been extremely rapid; e.g., the multinational pharmaceutical company AstraZeneca now applies the Kerr methodology to 90% of their relevant candidate compounds. Additional impact has been achieved by Strem Chemicals who have been manufacturing and marketing the catalysts worldwide since October 2012. Even in that very short period, multiple sales have been made on three continents providing economic benefit to the company.
The Abraham solvation parameter approach developed at UCL has become integral to the work carried out by drug discovery teams at [text removed for publication] and other major pharmaceutical companies, as well as research and development groups at international chemical companies including Syngenta and [text removed for publication]. It enables chemists to predict physicochemical and biochemical properties of chemicals, including drugs and agrochemicals, rapidly and efficiently, without the need to conduct time-consuming experiments. The method helps drug discovery teams to identify and optimise the most promising compounds, and often results in fewer compounds being made before a candidate is selected, saving time and resources. The approach has been integrated into software used for drug discovery [text removed for publication].
The development of new paradigms for toxicity testing has benefitted the Scottish economy and population in Tayside through two biotechnology companies which, between them, employ up to 40 staff and have had a combined turnover of some £15M over the last five years. The benefits extend to the international pharmaceutical, cosmetic, chemical and consumer product industries, which have gained access to innovative new methods for safety testing at a time of acute need for more predictive methods to evaluate drug safety and better in vitro tests for consumer products. Patients and consumers in Europe and worldwide have benefitted indirectly from improved risk assessment of drugs, consumer products and environmental contaminants.