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Subcutaneous allergen immunotherapy is highly effective in hayfever sufferers who fail to respond to anti-allergic drugs, but carries the risk of severe allergic side-effects. Professor Durham's group at Imperial College have defined the mechanisms and shown that sublingual tablet immunotherapy is an effective, safer alternative that induces long-term disease remission. The tablet approach is now widespread in Europe and is being successfully extended to other allergies (housedust mite) and internationally (ragweed allergy in USA and Japanese Cedar pollen allergy). The work is quoted in guidelines internationally and regulatory bodies now recognise the disease-modifying potential of immunotherapy and its ability to induce long-term remission.
Between 1995 and 2004 researchers at Imperial College developed a T cell peptide allergy vaccine in an attempt to improve the quality of life of millions of allergy sufferers worldwide. A spin-out company (Circassia Ltd) was founded and subsequently sold to Circassia Holdings Ltd, a clinical-stage specialty biopharmaceutical company based in Oxford, UK. Circassia Holdings Ltd has raised £98 million of funding since 2008 and has developed a pipeline of products to treat common allergies. In October 2012 the lead product ToleroMune® Cat entered a phase III clinical study involving 85 clinical sites across the USA, Canada and Europe and enrolling 1186 patients in the largest single field study ever undertaken in immunotherapy. Circassia currently employs 25 highly skilled people in-house with an outsourced business model giving employment to an estimated further 200 people.
King's College London (KCL) research has revealed that children who eat peanuts in infancy have a lower risk of peanut allergy than those who do not. This finding, and the associated research, has had significant national and international impact, as it led to a marked change in UK, European and American guidelines, such that they no longer discourage the introduction of peanuts to the infant diet. High profile coverage in scientific, government and lay press has widely disseminated this information.
An additional impact of the work was the development of the KCL Allergy Academy. This has become a large educational programme which each year reaches more than 1000 healthcare practitioners, plus patients and parents.
Sumbayev and colleagues have shown that gold nanoparticles represent an excellent platform for the specific delivery of drugs, targeting the HIF-1 biochemical pathway as a novel therapeutic target for diseases such as allergy, leukaemia and other autoimmune disorders. Two international, non-academic institutions have altered the direction of their work as a result of this research and two SMEs have revised their operational procedures and invested in the applied research that derives from this work.
Ongoing research by the University of Southampton has led to significant advances in the understanding of respiratory diseases, for which the dearth of available treatments had health repercussions on a global scale for many years. The formation of a spin-out company, Synairgen, has enabled the discovery and development of new therapeutics, the filing of several major patents in the UK, the US and Asia and external collaborations with industry and government funders. These continuing developments are key to tackling conditions that affect millions of sufferers in the UK alone and which, according to some estimates, cost the NHS £2.6bn every year. The research has given rise to more than £16m in follow-on funding from the NIHR and the MRC for further studies into the treatment of respiratory illnesses.
T lymphocytes recognise antigens in the form of an HLA-peptide complex. HLA-peptide tetramers consist of a fluorescent HLA protein and peptide which together bind to, and therefore identify, T cells that recognise this HLA-peptide complex. As such they have proven to be a revolutionary reagent in immunology. Professor Paul Moss at the University of Birmingham has played an integral role in the clinical and commercial application of tetramers, particularly around the cytomegalovirus (CMV)-specific immune response in the context of monitoring immune recovery after transplantation and pioneering a new approach for cellular immunotherapy. The impact of this research relates to the clinical management of CMV infection in immunosuppressed patients and the creation of Cell Medica, a UK Biotech company pioneering tetramer-based cell therapy, thus demonstrating impact on clinical practice and the UK economy.
Southampton research has been central to the development and international licensing of one of only two novel asthma therapies in the last 30 years, transforming asthma control and survival for severe allergic asthmatics.
Key studies by the Southampton Group have underpinned the development of immunoglobulin (Ig)-E as a key therapeutic target for controlling allergic asthma, with the Southampton-led first-in- man safety and efficacy trials critical to the registration of the anti-IgE therapy, omalizumab.
This contribution also generated significant inward investment in UK R&D and opened up wider investigation of anti-IgE therapy in a broad range of atopic and inflammatory indications.
Improved approaches to the management of asthma treatment in children, new NHS and BUPA healthcare guidance and changes in UK media attitudes have arisen from fundamental and clinical research at Brighton into the effects of genotype variation on responses to asthma medicines in children. Direct clinical benefits in quality of life resulted from the first-ever randomised clinical trial on genotype specific treatments for asthma. The subsequent worldwide media debate led to wider professional and public understanding of genetically-directed treatment choices and personalised medicines, with particular impact on parents of children with asthma.
Asthma and Chronic Obstructive Pulmonary Disease (COPD) are common, global diseases which cause considerable morbidity and mortality. Worldwide, around 235 million people suffer from asthma, while COPD accounts for 3 million, or 5% of all, global deaths, according to the World Health Organization (WHO). The relationship between inflammation and airway dysfunction is central to an understanding of their pathogenesis and treatment. The respiratory medicine group in the Department of Infection, Immunity and Inflammation has shown that optimal management of these conditions requires measurement of airway inflammation to stratify treatment regimes, an approach incorporated into national guidelines in 2012. In the late 1990s the group characterised a new clinical syndrome: `eosinophilic bronchitis', which is one of the commonest causes of chronic cough. The group's work has helped to launch a new class of drugs for asthma and to change the conceptual framework by which anti-inflammatory drugs for asthma are being developed.
Mouse disease models provide an invaluable tool to the medical sciences, underpinning the understanding of disease mechanisms and the development of therapeutic interventions. A new cultivation protocol for deriving mouse embryonic stem (ES) cells was developed by Dr Nichols between 2006 and 2009. This has facilitated the production of ES cells from disease model mice that can be manipulated in vitro and used to establish modified transgenic mice with the required genetic profile, in a single generation. This method reduces the number of mice needed, as well as associated costs and staff time, by 90%. Dr Nichols has trained industry delegates from international transgenics companies and transgenic facility managers in the new technology. As a consequence, a minimum of 26820 fewer mice have been used in experiments, and a minimum of £536k have been saved since 2009.