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The Farndale group have identified fragments of collagen, synthesised and assembled in active, triple-helical conformation, for use as ligands to manipulate platelet function. As a result of this work, the fragment Collagen-Related Peptide (CRP) is included in British Committee for Standards in Haematology guidelines as a platelet agonist for the diagnosis of platelet defects. The group has also synthesised triple-helical collagen peptide libraries and used them to map binding of cells or proteins to collagen more widely. The peptides are made and distributed by the Farndale lab, generating income through sales and licencing, and are used internationally by companies and hospitals to develop diagnostics and for high-throughput drug discovery. Prof Farndale also acts as a consultant for companies developing diagnostics.
Many clinically-useful natural products fall into the class of polyketides. From 1993, research led by Professors Leadlay (Biochemistry) and Staunton (Chemistry) on polyketide biosynthesis pathways led to the foundation of the spin-out company Biotica Technology Ltd in 1996. Between 2008 and 2013 the company provided continuous employment for on average 15-20 highly-skilled scientists, and attracted additional investments of £4.43M. Its follow-on company Isomerase Therapeutics Ltd, founded by ex-Biotica researchers with Leadlay's support in 2013, has acquired compounds, strains and IP from Biotica. Using the methods developed in the University by Leadlay and Staunton, Biotica developed a HepC antiviral therapy, sold in 2013 to NeuroVive Pharmaceuticals AB and currently entering pre-clinical toxicology tests. Biotica have also licensed their technology to a number of companies globally, including GSK and Amyris.
Research on the anatomy, physiology and palaeoecology of pterosaurs by the Palaeobiology Group at Portsmouth University has had a wide and acknowledged impact, underpinning the creation and production of block-buster and pioneering television and film productions worldwide. The impact of this work is recognised by Sir David Attenborough, and by the producers of such TV successes as Walking With Dinosaurs and Flying Monsters 3D. These award-winning productions, highlighting our work, have reached a global audience and supported the generation of millions of pounds by the UK TV and film industry. Whilst the income generated is highly significant, perhaps their greatest impact lies in fostering a positive view of science, particularly in young audiences, by bringing cutting-edge evolutionary science direct to the World's film and TV screens.
Response to treatment is the most important prognostic factor for a cancer patient. Conventional morphological imaging methods do not give an early indication of treatment response. Professor Kevin Brindle and colleagues demonstrated how hyperpolarised 13C magnetic resonance spectroscopic imaging (MRSI) could be used to determine treatment response in preclinical animal models of disease, and have identified metabolites that facilitate this imaging, which are now being used in clinical trials. As a direct result of this work, GE Healthcare founded a spin-out company that commercialises the hyperpolarised 13C-MRSI technology. Three hyperpolarisers, that can produce metabolites containing hyperpolarised 13C, have been sold, and a further 10 are on order, at a sales value of $2.2M / £1.41M each. Revenue and employment have been generated in the UK at Oxford Instruments, who build the cryomagnets for the hyperpolarisers.
The myeloproliferative neoplasms (MPNs) are chronic myeloid malignancies. Research led by Professor Green at Cambridge University reported that many MPN patients carry a JAK2V617F mutation and identified JAK2 exon 12 mutations associated with an MPN variant often previously diagnosed as idiopathic erythrocytosis. These outcomes led to tests for JAK2 mutations being established in the Eastern Region Haemato-oncology Diagnostic Service (Addenbrooke's hospital), providing a paradigm for other UK molecular diagnostic services. Tests for JAK2V617F and exon 12 mutations have greatly simplified, and improved the accuracy of, the diagnosis of MPN patients world-wide, and are now firmly embedded as front-line tests in national and international guidelines.
Members of the Pharmacology Research Group identified hitherto unknown properties of G protein Coupled Receptors (GPCRs): that ligands can signal differentially through both G-protein-coupled and β-arrestin pathways. This led to the concept of GPCR `biased signalling' and development of fluorescent reporters to quantify β-arrestin signalling. These discoveries have been adopted widely by the pharmaceutical industry, attracting R&D investment and collaborative research funding, to drive discovery of new drugs operating through `biased signalling'. The commercial opportunity has also been exploited by screening reagent providers and contract screening organisations. These discoveries will ultimately produce better drugs to treat GPCR-based diseases to improve human health.
Research led by Dr. Peter Richardson in the Department of Pharmacology led to the development of an A2A adenosine receptor antagonist (istradefylline) for the treatment of Parkinson's disease. In 2001, Dr Richardson founded the spin-out company Cambridge Biotechnology (CBT) to develop these drugs. A pH-sensitive adenosine A2A receptor agonist is now being developed for the treatment of neuropathic pain, with one product licensed for use in Japan in 2013 (Nouriast). Small-molecule leptin mimetics as potential anti-obesity drugs were also developed, initially by CBT and since 2009 by Astra Zeneca following acquisition of the research programme. CBT has undergone a number of high-value acquisitions, by Biovitrium, Proximagen, and most recently Upsher-Smith. It continues to operate as a wholly-owned subsidiary, employing 30-35 people from 2001 to the present.
Sudden cardiac death causes 4.5 million deaths worldwide each year many of which could be prevented by implantable cardioverter defibrillators (ICDs), but these also carry risks. Research in the groups of Huang and Grace has led to diagnostic assays offering three times the predictive accuracy of current approaches in guiding cardiologists concerning indications for ICD implantation. The assay has been clinically trialled; since 2008, through the trial, the lives of three patients identified by the assay as at high risk were saved. Further work led by Grace and colleagues provided an improved, subcutaneous ICD (SICD); Grace also participated in a US-based clinical trial (NCT00399217) providing the evidence required for FDA approval supporting also later inclusion into NICE guidance. Since 2008 the SICD has been implanted in over 2500 patients in 16 countries.
This research into rich donors in the UK has impacted on the policies of both governmental and non-governmental bodies. Government policy shapes and incentivises philanthropic behaviour (e.g. through tax incentives), whilst charity sector bodies influence philanthropic norms and build trust: both have used this research to guide their policy and practice. Examples include the influence of the research on the content of the UK Government's Giving White Paper (2011); the decision to abandon the proposed cap on charity tax relief (2012 Budget); and the work of bodies who promote fundraising and philanthropy, for example, the Institute of Fundraising, Philanthropy UK and Charities Aid Foundation (CAF).
Research conducted at the University of Bristol since the late 1990s has pioneered the development of over 60 chemical probes that are selective for individual ionotropic and metabotropic glutamate receptors. The development of these probes has led to numerous commercial impacts, including: the establishment of two companies, which both sold during the assessment period for a combined value of £85 million, and sales revenue for global providers of biochemicals. This research has also stimulated considerable industry investment in drug development.