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Highly Active Anti-Retroviral Therapy (HAART) is a combination of drugs used to effectively control HIV infection. Since 1987 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) had been used in HAART combinations to specifically target HIV-1 reverse transcriptase, however, resistance and side effects soon prompted the need for an alternative. In 1998, University of Oxford Professors David Stuart and David Stammers provided the first detailed structural framework to facilitate the design of a highly effective alternative class of drug, the Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs). NNRTIs have since been developed for clinical use, impacting the pharmaceutical industry and profoundly improving the quality of life of patients.
Viral infections pose a significant risk of long-term disease and death to cats. In Europe alone, over 30 million domestic cats are vaccinated each year against three core pathogenic viruses. Research performed at the University of Glasgow has systematically supported the development of key technologies against major feline viral diseases. This work has delivered incremental but wide-reaching benefits to veterinary healthcare and animal welfare by providing: (i) reagents used in the diagnostic industry; (ii) viral screening services for big cat conservation programmes; (iii) developmental input into the creation of one of the most efficacious and widely used vaccines against feline leukaemia virus; (iv) testing of feline vaccines for efficacy and safety; and (v) development of best practice guidelines and training for veterinary practitioners on feline viruses.
Oxford BioMedica is an established company in the rapidly growing field of gene therapy. Founded by Professors Alan and Sue Kingsman from the Department of Biochemistry at the University of Oxford, it develops, commercialises and manufactures safe and effective vectors for use in gene therapy. Its vector system, known as LentiVector®, is based on the Kingsman's research into the biology of a family of retroviruses known as lentiviruses. The company has a portfolio of over 60 patent families, employs over 80 people and has raised almost £150 million since its foundation. Oxford Biomedica's partners include the major pharmaceutical companies Novartis and Sanofi and its vectors are being used in clinical trials to deliver treatments for leukaemia, Parkinson's disease and disorders of the eye.
Research carried out by LSHTM into the effects of male circumcision on HIV prevention has led to important policy recommendations by WHO and UNAIDS, the joint UN Programme on HIV/AIDS. The research showed a strongly reduced risk of HIV infection among circumcised men, and modelling studies estimated that male circumcision programmes in 13 priority countries in Africa could avert 4m HIV infections by 2025. Members of the research team serve on key international advisory groups, and these results have been widely used to underpin international policy guidelines.
In sub-Saharan Africa, 22 million people live with HIV/AIDS. Annual mortality is 1.5 million and sexual transmission accounts for ~90% of new infections. Young women are disproportionately affected due to socio-cultural issues. Seeking to empower them with an urgently needed female-initiated protective method, Malcolm & Woolfson developed the first antiretroviral (AR) microbicide vaginal ring (VR), which provides slow, continuous release of dapivirine for long-lasting protection against vaginal HIV transmission. Consequently, global microbicide development strategies were transformed, with the focus shifted from immediate-use gels to long-acting VRs. In August 2012, the dapivirine VR commenced final stage (Phase III) clinical trials in Africa.
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:
Dalgleish proposed a programme to develop thalidomide analogues for their immunomodulatory and anti-neoplastic actions. Working with a small start-up company, Celgene, several analogues including lenalidomide and pomalidomide were developed and entered clinical trials. Both drugs significantly prolong patient survival in myeloma and myelodysplasia and have received FDA and NICE approval for these purposes. Celgene has grown into a large multi-national company with over 5000 employees. Lenalidomide sales were $3.8 billion in 2012.
Researchers from St Georges have evaluated and optimised anti-fungal therapy for cryptococcal meningitis, the commonest cause of adult meningitis in sub-Saharan Africa. They have developed a "screen-and-treat" strategy to prevent the development of clinical disease in HIV-positive patients, and with collaborators developed and tested a novel point-of-care diagnostic test. These advances have led to changes in and development of a series of international guidelines and application of these new strategies in parts of Africa. A case for reduced costs of amphotericin was advanced by the group who were instrumental in reducing these costs in South Africa, allowing wider drug provision.
UCL investigators have been at the forefront of characterising and assessing HIV drug resistance since 1990, soon after the very first HIV drug was licenced. There are currently more than 25 drugs available, and our work over the last 23 years has directly determined how best these therapies are used, and monitored in infected patients. We have extended our work to a global perspective, in conjunction with the current rollout of antiretroviral therapy to areas of the world devastated by the epidemic - work which now informs guidelines of the World Health Organisation (WHO), and has resulted in a marked reduction in mortality.
Recent outbreaks across Europe of Bluetongue, a viral disease particularly affecting sheep, have driven research at LSHTM by Professor Polly Roy and her team, resulting in the Bluetongue virus (BTV) becoming one of the best understood viruses at the structural and molecular levels. The research has ultimately enabled the creation of several promising new vaccines. In addition the Roy group has contributed towards exploiting virus-like particles (VLPs) as a method to produce safe vaccines against human and animal viral pathogen. The most advanced example is a BTV vaccine for livestock, which is manufactured by Boehringer Ingelheim (BI).