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Cancer research at the University of Salford focuses on developing new and improved treatments for cancer, particularly for children with cancer, demonstrating the following impact:
Southampton research underpins the clinical development of a new class of anti-cancer monoclonal antibodies (mAb), such as anti-CD40, anti-CD27 and anti-CD20. The most advanced is a next generation, fully human drug, ofatumumab (commercialised by GlaxoSmithKline/Genmab; trade-name Arzerra) approved in Oct 2009 to treat advanced chronic lymphocytic leukaemia. Its approval was based on a 42% response rate in patients who had failed current `best in class' treatment. Arzerra is now a multi-million dollar drug, launched in 26 countries (and growing) and is being used in 19 on-going clinical trials worldwide for diseases ranging from lymphoma to rheumatoid arthritis and multiple sclerosis. Southampton's work has inspired follow-on funding from government and industry in excess of £12m.
Psoriasis is a chronic inflammatory skin disorder affecting up to 2.5% of the world's population, approximately 30% of whom eventually develop psoriatic arthritis, which can lead to debilitating long-term health problems. Current therapies are limited owing to side effects or reductions in efficacy. Prof Miles Houslay, University of Glasgow has performed internationally recognised research on drug targets to alleviate the symptoms of inflammatory skin conditions. Working with Celgene, Houslay identified lead compounds and assays to screen promising early compounds for the treatment of psoriasis and psoriatic arthritis for clinical development. This identified the lead compound (apremilast), which was subsequently developed by Celgene. Between 2010 and 2013, phase III trials on apremilast have validated it as a safe, clinically effective oral drug, on the basis of which apremilast was submitted for regulatory approval of its use in patients with psoriatic arthritis to the health authorities of the USA and Canada in March 2013.
Dalgleish proposed a programme to develop thalidomide analogues for their immunomodulatory and anti-neoplastic actions. Working with a small start-up company, Celgene, several analogues including lenalidomide and pomalidomide were developed and entered clinical trials. Both drugs significantly prolong patient survival in myeloma and myelodysplasia and have received FDA and NICE approval for these purposes. Celgene has grown into a large multi-national company with over 5000 employees. Lenalidomide sales were $3.8 billion in 2012.
ProTide technology, discovered by the McGuigan team at Cardiff University, is a pro-drug strategy with proven capacity to generate new drug candidates for nucleoside-based antiviral and anti- cancer indications. In the assessment period the McGuigan team has attracted more than £2 million direct research funding through sustained collaborations on ProTide technology with global pharmaceutical companies and smaller biotech firms in the USA and Europe. In the same period, either through working directly with Cardiff or by independent adoption of McGuigan's research, eight ProTide entities have progressed to clinical trials as cancer, HIV and hepatitis C treatments. The technology is demonstrating significant commercial impact for companies with ProTide-based drug candidates.
Chronic, debilitating diseases such as arthritis, chronic obstructive pulmonary disease (COPD) and inflammatory bowel disease (IBD) could potentially be treated by damping down the underlying inflammation and therefore improving the quality of life of sufferers. Nrf2 is a protein that prevents inflammation when activated and many researchers have sought to manipulate its activity as a potential therapeutic strategy. However, this has had little success, due to a lack of suitable biochemical tools. We describe here the Nrf2-activating peptide TAT14, which was developed in Pharmacy and is now being marketed by biotech companies to study this important pathway.
The Progeria Research Team at Brunel has been researching Progeria for over 10 years. Interestingly, they have close contact with Progeria families and support them by helping parents make decisions about drug treatments available in clinical trials and providing scientific information about the disease and the team's research. The Progeria research has allowed the team to engage directly and positively with individuals and communities that raise money and awareness for Progeria research in interesting and entertaining ways. The team have raised public understanding and awareness of Progeria locally, nationally and globally. This has been done directly, and also by facilitating the production of a film and a TV programme about the disease.
Edinburgh Napier University is internationally recognised for its research into the mechanisms that drive the adverse health effects of inhaled particles. Pharmaceutical company GlaxoSmithKline (GSK) required early understanding of the likelihood that inhaled drug particulates, used in the treatment of asthma, would evoke an adverse biological response, thus compromising the development of any novel drug. Through collaboration, via a Knowledge Transfer Partnership (KTP), we were able to develop improved in vitro methodologies to study toxicity and, thus, predict pathologies reported in vivo with the aim of reducing both the use of animals and pre-clinical drug attrition.
Research conducted by a multidisciplinary team of oncologists and scientists at the University of Southampton has driven major advances in lymphoma care, leading to the development and standardisation of effective new antibody treatments and optimal drug regimens. Through their direction of international clinical trials, they have influenced care for Hodgkin and Burkitt lymphoma in the UK and internationally, affecting all stages of patient-experience from diagnosis to treatment. Their findings underpin significant improvements in survival and quality of life for the 14,000 people affected by lymphoma in the UK each year.
All new drugs are required to undergo cardiac safety testing to avoid dangerous side effects on contractility and excitability. Of particular concern is the risk of developing a lethal arrhythmia from inhibition of hERG (human Ether-à-go-go-Related Gene) potassium channels. The Bristol laboratory of Professor Hancox and colleagues demonstrated the utility of hERG-transfected mammalian cell lines for investigation of hERG-related effects and risk. Now most drug discovery programmes utilise hERG screens as part of an integrated assessment of cardiac risk (as recommended by the FDA and MHRA). Second, their work linked hERG inhibition to cardiac risk for certain psychotropics (and other agents) that have been either withdrawn or now carry warnings as to their cardiac safety.