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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.
Research by Professor Grassly and colleagues at Imperial College on the epidemiology of poliovirus and the efficacy of new vaccines has played a critical role in the thinking and strategy of the Global Polio Eradication Initiative (GPEI). This research has supported the introduction of new vaccines, guided the timing and location of vaccination campaigns and influenced polio `endgame' policy. This is documented in the GPEI Strategic Plan 2010-2012, where Imperial research informed 2 of the 4 `major lessons' concerning poliovirus epidemiology described in the executive summary that led to changes in the programme. The research has also informed our understanding of mucosal immunity induced by oral poliovirus vaccines, and led to two clinical trials of the potential role of inactivated vaccine to boost mucosal immunity. Results from one of these trials were used to support the recent World Health Organisations (WHO) recommendation for universal vaccination with inactivated vaccine following the switch to bivalent oral vaccine in routine programmes.
Imperial College preclinical studies guided the desired selectivity profile for long-acting muscarinic receptor antagonists (LAMA). Binding, functional and clinical studies from Imperial laboratories were the first to demonstrate the long duration of tiotropium bromide (Spiriva®) in human tissue, and confirmed its long duration of action in patients and established it as the first-line treatment for chronic obstructive pulmonary disease (COPD). Tiotropium has had a beneficial impact on the management of COPD and is incorporated into the major international treatment guidelines. It improves symptoms, reduces exacerbations and mortality, and provides a cost-effective therapy. Imperial have also produced the first pre-clinical and clinical data for the next LAMA in development (glycopyrrolate, Seebri®), which has recently been marketed. Our profiling of tiotropium has also led to the development of several novel LAMA.
Temozolomide is a major UK anti-cancer drug development success story. Following chemical synthesis at Aston University, early clinical evaluation of temozolomide carried out at Imperial College optimised how temozolomide was scheduled and delivered to patients to ensure maximum efficacy balanced acceptable side effects. Imperial's early trials demonstrated how the drug could be used effectively to treat patients with a type of brain cancer, glioma, and was pivotal to its subsequent market licensing. ESMO and NICE guidelines recommend temozolomide for use in patients with recurrent glioma and for patients with newly diagnosed Grade IV glioma. Glioma is a relatively rare cancer yet annual sales of temozolomide have been in excess of £900 million per year since 2009. Temozolomide given during and following radiotherapy is now standard of care for glioma and has improved survival compared to previous treatments or radiotherapy alone.
Research undertaken within Imperial College showed that corticosteroid resistance in inflammatory diseases, such as chronic obstructive pulmonary disease (COPD) and severe asthma, is explained by reduced histone deacetylase-2 and that reversal of this resistance is possible with theophylline (in low clinical doses) and PI3Kδ inhibitors, which restore HDAC2 function. This led to the founding of a spin-out company RespiVert to develop potent inhaled inhibitors of PI3Kδ. The company has been very successful in finding such new molecules, which have proven to be safe in Phase I studies. RespiVert was acquired by Johnson & Johnson in 2010 and Phase II studies are now in progress in COPD and severe asthma.
Research by the University of Aberdeen has helped deliver a turnaround in the medical advice given to pregnant women in the UK regarding the consumption of peanuts. Previous Department of Health advice was for pregnant women with a personal or family history of allergic disease to avoid eating peanuts in order to prevent allergy in their offspring. However, the Aberdeen research into neonatal immune responses demonstrated that laboratory responses of cord blood mononuclear cells exposed to allergens in vitro were unrelated to antenatal allergen exposure. The findings and resulting change in health advice attracted wide international attention.
Therefore this research has had impact in: health and welfare by changing dietary guidelines, increasing public awareness of a health risk public behaviour and influencing decisions and care practices by a health service.
Research performed by the University of Oxford has led to increased protection against meningococcal meningitis, through childhood immunisation in the UK and internationally. Around 600,000 infants each year receive meningococcal vaccines, which prevent up to 1,000 cases of meningitis per annum. Research into the immune responses to polysaccharide conjugate vaccines has changed policy by leading to the introduction of new meningococcal C vaccines in early childhood and booster vaccination in adolescents. Oxford University research has also led to the planned use of vaccines against serogroup B meningococcal disease, which have been licensed and recommended for the prevention of disease in high-risk individuals, and broader use is under consideration.
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.
Research at the University of Manchester (UoM) has led a step-change in respiratory care for airway disease from oral to novel inhaled therapies targeted at asthma and chronic obstructive pulmonary disease (COPD) patients worldwide. UoM researchers carried out >250 studies, partnered industry to deliver >15 new inhaled drug formulations to market and were the first to test novel CFC-free inhalers. UoM led the development of global guidelines that influence better diagnosis and management of airways diseases. Through leadership within the Montreal Protocol since 1995, UoM researchers coordinated the safe global transition to CFC-free inhalers for ~200m patients with asthma and COPD, whilst protecting the ozone layer and climate.
Questions about the benign or malignant nature of liver tumours are common and pressing since they determine how the patient is managed. Benign masses are frequently encountered; they usually do not require intervention but are easily mistaken for malignancies with conventional imaging methods. Work at Imperial College demonstrated that microbubble contrast agents have the special property of lingering in both normal liver tissue and in benign solid masses, whereas malignancies do not retain microbubble. The discovery of this property at Imperial has led to their use worldwide as a diagnostic tool. In 2012 NICE recommended their use as being cost-effective for this use.