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Individuals with Xeroderma pigmentosum (XP) are extremely susceptible to sunlight-induced skin cancers and, in some cases, develop neurological problems. Alan Lehmann has developed a cellular diagnostic test for this disorder. This test is now conducted as an integral part of a multi-disciplinary XP specialist clinic in London, which was established as a direct result of Alan Lehmann's research in Sussex and which has led to the improved diagnosis and management of the disorder and an improved quality of life for affected individuals.
Through their study of DNA polymerases from organisms of the domain archaea, researchers at Newcastle University and University College London identified the mechanism by which these organisms avoid potentially damaging mutations in their DNA. As a consequence of this work they invented a novel genetically-engineered DNA polymerase. This enzyme has been patented and is the world's only high-fidelity, proofreading DNA polymerase that efficiently reads through uracil in the polymerase chain reaction (PCR). PCR is a very widely used technique in biomedical research. An international bioscience company [Text removed for publication, EV d] signed a licensing agreement with Newcastle University in 2008 to market the enzyme, and total sales since 2008 exceed [Text removed for publication, EV d]. Further commercial exploitation has begun through licensing agreements with other major companies.
Research by Professor Steve Jackson led to the discovery of synthetic lethality as a means of selectively targeting cancer cells, and to Jackson founding KuDOS Pharmaceuticals to translate this research into therapies. This novel approach has changed the way pharmaceutical companies develop cancer therapeutics and has led to several drugs reaching pre-clinical and clinical development. The most advanced of these (olaparib, a PARP inhibitor originally developed at KuDOS and acquired by Astra Zeneca) is now entering Phase 3 trials and registration in Europe. In 2011, Jackson founded MISSION Therapeutics Ltd, to extend the synthetic lethality concept into targeting deubiquitylating enzymes to selectively kill tumour cells.
Research by Professor David Brook on inherited disorders has made a major contribution to the human genetics field. The work involved gene identification and mutation detection for genotype/phenotype correlation analysis in patients, which has led to the development of diagnostic tests for inherited conditions including myotonic dystrophy type 1 (DM1), Holt-Oram Syndrome (HOS), and campomelic dysplasia (CD). The tests have benefitted patients in the UK and throughout the rest of the world and in many cases they have been used as the definitive diagnostic measure. The assays developed have also been used in affected families for prenatal diagnosis to enable informed reproductive decisions.
Research at the UCL School of Pharmacy has positively influenced healthcare in startle disease/hyperekplexia, a rare disease that affects humans and several animal species, including dogs, horses and cattle. The identification and functional characterisation of mutations in genes involved in human startle disease by researchers at the School has improved genetic diagnostics and patient care. Our research on startle disease in cattle and dogs has also led to new non- invasive diagnostic tests that have alleviated animal suffering and reduced negative economic impacts on farmers. Overall, our findings have been translated into tangible benefits for the human and animal populations affected by this disease and have changed the way in which the disease is diagnosed and treated. We have also significantly increased the awareness of this rare disorder by communicating with academics, healthcare and veterinary professionals, and the general public.
Genetic skeletal diseases (GSDs) are an extremely diverse and complex group of genetic diseases that affect the development of the skeleton. Although individually rare, as a group of related genetic diseases they have an overall prevalence of at least 1 per 4,000 children, which extrapolates to a minimum of 225,000 people in the European Union. This burden in pain and disability leads to poor quality of life and high healthcare costs. GSDs are difficult diseases to diagnose and there are currently no treatments, therefore, arriving at a confirmed diagnosis is vital for clinical management, psycho-social support and genetic counselling.
Research conducted at the University of Manchester (UoM) has had a major influence on establishing the correct diagnosis of specific GSDs by the discovery of causative genes and mutations and the subsequent development of accurate and reliable DNA testing protocols. This has significantly improved both accuracy of, and access to, genetic testing in the UK, Europe and worldwide.
High-throughput genotyping has revolutionised the genome-wide search for associations between genetic variants and disease. Professor Sir Edwin Southern of the University of Oxford's Biochemistry Department invented the highly cost-effective array-based method of analysing genetic variation based on hybridisation between probes and samples on glass slides or `chips'. The spin-out company Oxford Gene Technology (OGT) founded by Southern in 1995 licenses the patent to manufacturers of `single nucleotide polymorphism (SNP) chips', including Illumina and Agilent, a global business exceeding $500M per year. Southern has continued to refine and extend this technology to increase its speed, efficiency and cost-effectiveness. This revolutionary technology has widespread applications such as prediction of individual risk, development of new drugs, provision of personalised treatments, and increased cost-effectiveness of clinical trials. Licence revenues fund R&D within OGT, and endow charitable trusts supporting primary school science education in the UK and crop improvement in the developing world.
As a result of research from Oxford's Professor Andrew Wilkie, accurate genetic diagnostic tests are now available for over 23% of all craniosynostosis cases nationally and internationally, leading to improved family planning and clinical management of this common condition worldwide. The premature fusion of cranial sutures, known as craniosynostosis, is a common developmental abnormality that occurs in 1 in 2,500 births. Over the past 20 years, the University of Oxford's Clinical Genetics Lab, led by Professor Wilkie in collaboration with the Oxford Craniofacial Unit, has identified more than half of the known genetic mutations that cause craniosynostosis and other malformations of the skull.
Research from the University of Oxford's Clinical Genetics Laboratory initiated the introduction of an upper age limit of 40 years for sperm donors in the UK and internationally and led to increased public awareness of the effect of paternal age in the transmission of inherited disease. Oxford researchers, led by Professor Andrew Wilkie, were the first to describe the exclusively paternal transmission of de novo mutations, in a rare craniofacial disorder called Apert Syndrome; they also showed that the accumulation of such mutations leads to a disproportionate risk of disease transmission with age. By showing that the frequency of mutations increases with paternal age, this research contributed to important changes in clinical practice relating to sperm donation. This has also had a significant cultural impact, as the research and its clinical outcomes have challenged public perceptions of paternal age.
Researchers at the University of Sheffield developed a novel tailored therapy for some forms of breast cancer. This was the first example of the selective killing of a tumour using an inhibitor of a DNA repair enzyme (PARP) to induce synthetic lethality, heralding an era of personalised cancer therapy. The discovery was patent protected and development rights sold to Astra-Zeneca who undertook successful phase I and II clinical trials. Disclosure of the findings stimulated intense investment in research and development and has revolutionised approaches to cancer therapy. There are now eight PARP inhibitors in phase I to III clinical trials (92 currently listed involving several leading pharmaceutical companies and thousands of patients) targeting a wide range of tumour types.