Summary of the impact

Research conducted at the University of Bristol has influenced the direction of research and investment of pharmaceutical companies and led to improved patient outcomes in preliminary clinical trials. Myocardial infarction (heart attack) and stroke are a major health issue for Western society and a frequent cause of premature death. Treatment of these conditions involves procedures that restore blood flow to the tissues, but there is a significant risk of further tissue damage when the blood supply returns — known as reperfusion injury — due to inflammation and oxidative stress. Since 1993, Professor Halestrap has conducted pioneering work on the role of the mitochondrial permeability transition pore (MPTP) in reperfusion injury. In 1995, he demonstrated that inhibition of the MPTP protects the rat heart from reperfusion injury and in 1998, with his collaborators he demonstrated protection in rat brains. His studies helped establish the MPTP as the most promising target for developing drugs against reperfusion injury. In 2000, pharmaceutical companies started investing in the research and development of such drugs. Subsequently, this has led to formal contracts with seven pharmaceutical companies, a patent and seven clinical trials with improved outcomes for patients in an initial Phase II trial leading to a large ongoing multi-centre Phase III trial.

Summary of the impact

Research carried out within Imperial's Life Sciences department led to a collection of new kit solutions to screen the crystallisation conditions of various membrane proteins. These screens were exclusively commercialized by Molecular Dimensions, a UK company, in 2002, 2003 and 2008 under license from Imperial College London. They are the primary screening kit in membrane protein crystallization that is commercially available. These screens have helped to screen the crystallization conditions of a wide range of membrane proteins, leading to many new structures. Molecular Dimensions has sold [text removed for publication] screens, worth more than [text removed for publication], to both academia and industry all over the world.

Summary of the impact

Bacillus species constitute an industrially-important group of bacteria that are used worldwide to produce carbohydrate and protein-digesting enzymes on a large scale. While the bacteria secrete native enzymes at an economically viable rate, generating strains of bacteria that could do the same for non-native enzymes has been an industry challenge. Researchers at Newcastle University have collaborated with industry since the early 1990s to study the mechanism of protein secretion in Bacillus. They discovered bottlenecks in the protein secretion pathway and used that knowledge to engineer more productive strains of bacteria. Since 2008, companies, including Novozymes (the world's largest manufacturer of industrial enzymes), have developed strains of bacteria, based on the Newcastle findings, for use in their manufacturing processes improving yields by more than four orders of magnitude in some cases.

Summary of the impact

Stem cells play an important role in drug discovery and development of therapeutic interventions. Differentiation (and maintenance) of stem cells into specialised cells is achieved by controlled application of specific, expensive growth factors.

Dr Hyvönen has developed an efficient method for producing highly purified, bioactive human growth factors from E.coli, reducing costs by up to 10-FOLD. tHE TECHNOLOGY HAS BEEN LICENSED TO A major international manufacturer of growth factors (PeproTech Inc.), and to a UK-based specialist stem cell company (CellGS Ltd), enabling them to implement new products and business strategies. Through a departmental facility, material is also being sold to external companies and Cambridge Stem Cell Consortium members. In addition, Dr Hyvönen has made his expertise available to biotech companies through consultancy.

Summary of the impact

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.

Summary of the impact

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:

• The development of RH1, a novel anticancer drug and a second generation novel agent, Es5, arising from RH1;
• Participation in clinical studies in paediatric and adult cancers with North West, UK and international partners in the health, charitable and commercial sectors to trial and develop the technologies;
• The establishment of spin-out company, Onco-NX to develop and exploit the technologies and IP arising from the research;
• The establishment of Kidscan, a University-based registered charity to support research into new and improved treatments for children with cancer and generating dedicated support for and commitment to cancer research among North West UK communities.

Summary of the impact

In 2003, researchers at the University of Dundee identified the tumour suppressor LKB1 as a critical upstream activator of AMP-activated protein kinase (AMPK), which provided the first link between AMPK and cancer. Metformin, the front-line therapy for type-2 diabetes, was already known to exert its beneficial effects through AMPK. An interdisciplinary collaboration at the University examined the link between metformin and cancer, and reported in 2005 that diabetics taking metformin had a reduced incidence of cancer. The impact has been clinical trials worldwide testing the benefit of metformin for cancer treatment, and development of therapeutics by pharmaceutical companies targeting this pathway.

Summary of the impact

Research on clinically important red blood cell membrane proteins has helped avoid unnecessary treatment of Rhesus negative pregnant women and enabled the early diagnosis of a rare kidney disease. During the late 1990s, researchers at the University of Bristol, in collaboration with the Blood Service in Bristol, cloned, sequenced and characterised many red blood cell membrane proteins important for transfusion, including the Rhesus proteins and Band 3/AE1 (SLC4AE1 gene). The work on Rhesus proteins facilitated the use of less invasive genetic screening methods to ascertain whether treatment was required to avoid Haemolytic Disease of the Foetus or Newborn (HDFN). In the UK, 5,000 women have been screened since 2001. Within the first six months of implementation of a Danish national screening program in January 2010, 862 women avoided unnecessary treatment. Reducing unnecessary treatment of mothers has saved resources and avoided unnecessary exposure to human derived blood products. In addition, research that has identified specific SLC4AE1 gene mutations that cause the rare kidney disease called distal renal tubular acidosis has enabled the early diagnosis and treatment of the disease, resulting in improved outcomes for patients.

Summary of the impact

Professor Neil Barclay and Dr Nick Hutchings established Everest Biotech Ltd in 2000 in response to the increasing demand for high quality antibodies within the research community. This successful spin-out company has since become a major power in antibody research and production, a position reflected by its portfolio of more than 6,000 antibodies recognising human, mouse and rat proteins, and the generation of 60 new antibodies each month. With offices in the UK and Nepal, Everest Biotech Ltd also benefits one of the poorest communities in the world by providing additional income to hundreds of farmers in the Nepalese foothills.

Summary of the impact

The provision of effective and sustainable healthcare is a major challenge for society. In the developed world escalating costs are placing a huge burden on finite resources; in the developing world, where financial resources are often extremely limited, providing affordable healthcare is an even greater problem. One innovative route to help alleviate these problems is through drug redeployment, whereby existing drugs are employed in new ways to tackle serious diseases. Combining their knowledge of haematological disease gained from their research over the past 20 years together with a drug redeployment strategy, researchers in the School of Biosciences have developed and trialled new interventions for two blood cell cancers, Acute Myeloid Leukaemia (AML) and Burkitt's Lymphoma (BL), based on the administration of a combination of the lipid lowering drug Bezalip (Bez) and the female contraceptive Provera (MPA). As a result:

• Definitive significant outcomes have been demonstrated in terms of halting disease progression and / or diminishing disease load in patients suffering from AML and BL.
• Successful drug redeployment, on the basis of efficacy, absence of toxicity and low cost of drugs has been achieved.
• This intervention has created the means to reduce childhood mortality and improve the length and quality of life in areas of sub-Saharan Africa.