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HIV Associated Multicentric Castlemanā€™s Disease: Translating Biology to Improved Patient Survival

Summary of the impact

HIV associated plasmablastic multicentric Castleman's disease (MCD) has emerged as an uncommon disease over the last decade that is a significant cause of mortality in people living with HIV infection. Advances in our understanding of the epidemiology, virology and immunology of this disease led Professor Bower to recognise the potential for using targeted monoclonal antibody therapy. This has dramatically improved the survival of patients with MCD and is now advocated in the national treatment guidelines and is widely adopted in clinical practice globally. Moreover, the use of plasma Kaposi's sarcoma herpesvirus virus levels as a tumour marker for MCD has been developed.

Submitting Institution

Imperial College London

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Clinical Sciences, Oncology and Carcinogenesis, Public Health and Health Services

UOA01-07: Melioidosis: Managing Chronic Infection

Summary of the impact

Sustained research by the University of Oxford's Mahidol Oxford Tropical Medicine Research Unit in Thailand (MORU) has been the driving force behind the current World Health Organization recommendations for the management of acute and chronic infection in patients with melioidosis. This research has motivated improvements in treatments and provided new strategies to identify at-risk populations, enabling clinicians to make early diagnoses. Melioidosis is a major cause of severe illness in parts of Southeast Asia and there are increasing numbers of cases in India, China, and Brazil.

Submitting Institution

University of Oxford

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences, Medical Microbiology

A rapid blood-based diagnostic test for meningococcal disease adopted worldwide

Summary of the impact

Meningococcal meningitis is a life-threatening acute disease affecting 1.2 million people every year. Accurate and rapid diagnosis is essential for optimal patient response; however, bacterial culture tests are slow and undermined by the immediate administration of antibiotics, resulting in sterile cultures.

The Surrey team developed a rapid, non-culture-based diagnostic test for meningitis and septicaemia: this test is now routinely used for diagnosis of meningococcal disease worldwide, and was also instrumental in the implementation and monitoring of control measures for the disease, such as life-saving vaccination campaigns. Together these have contributed to the halving of adult mortality rates from meningitis worldwide.

Submitting Institution

University of Surrey

Unit of Assessment

Allied Health Professions, Dentistry, Nursing and Pharmacy

Summary Impact Type

Technological

Research Subject Area(s)

Medical and Health Sciences: Medical Microbiology

Defining the Role of Antiretroviral Therapy for Primary or Recent HIV Infection

Summary of the impact

The SPARTAC study (Short Pulse Anti-Retroviral Therapy at HIV Conversion) was a randomised clinical trial of short (12 weeks) or long (48 weeks) pulsed antiretroviral therapy (ART) at primary or recent HIV infection, compared to deferred therapy (standard of care). The trial has shown a significant effect of 48 weeks ART, compared to deferred therapy; 12 weeks ART had no effect. This definitive result from the SPARTAC trial has informed HIV treatment guidelines nationally and internationally; patients identified with primary or recent HIV infection are now recommended to commence ART, based in whole or part on the evidence arising out of SPARTAC. As a consequence of the SPARTAC trial, it is no longer ethical to undertake research amongst individuals with recent HIV infection without offering immediate ART.

Submitting Institution

Imperial College London

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Clinical Sciences, Medical Microbiology

Improving clinical care for lymphangioleiomyomatosis

Summary of the impact

Research at the University of Nottingham has defined the clinical phenotype and management of lymphangioleiomyomatosis, a rare and often fatal multisystem disease affecting 1 in 200,000 women worldwide. The group has led the development and evaluation of new therapies and diagnostic strategies which are now part of routine clinical care. The research has underpinned the transformation of this previously under recognised and untreatable disease into a condition recognised by respiratory physicians, with international clinical guidelines, patient registries, clinical trials, specific treatments and a UK specialist clinical service.

Submitting Institution

University of Nottingham

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services

UOA05-04: Miglustat: the first oral treatment for rare but devastating lysosomal storage disorders

Summary of the impact

Professor Platt and colleagues at the University of Oxford have developed the drug miglustat, the first oral therapy for rare lysosomal storage diseases. These are primarily neurodegenerative diseases that affect 1 in 5,000 live births, always leading to premature death. In 2009, miglustat became the first treatment to be licensed for treating neurological manifestations in Niemann-Pick disease type C (NPC). It is now prescribed for the majority of NPC patients worldwide, and has led to significant improvements in both life expectancy and quality of life. Miglustat was approved for type 1 Gaucher disease in 2002 and, since 2008, has proved an effective treatment for patients previously stabilised with enzyme replacement therapy; miglustat has the additional benefit of improving bone disease. Sales of miglustat since 2008 have generated CHF 315 million in revenues for Actelion, the company sublicensed to sell the drug.

Submitting Institution

University of Oxford

Unit of Assessment

Biological Sciences

Summary Impact Type

Technological

Research Subject Area(s)

Biological Sciences: Biochemistry and Cell Biology
Technology: Medical Biotechnology
Medical and Health Sciences: Cardiorespiratory Medicine and Haematology

Commercialisation of a Novel Diagnostic Test for Invasive Pulmonary Aspergillosis

Summary of the impact

Invasive pulmonary aspergillosis (IPA) is a frequently fatal disease of haematological malignancy patients, caused by fungi from the genus Aspergillus. Dr Christopher Thornton has developed and commercialised a novel point-of-care test for the diagnosis of IPA with an Aspergillus-specific monoclonal antibody (mAb) JF5 generated using hybridoma technology. Using this mAb, he has developed a lateral-flow device (LFD) for the rapid detection of Aspergillus antigen in human serum and bronchoalveolar lavage fluids (BALf) that signifies active infection. Commercial exploitation of the patented technology has been met through the establishment of a University of Exeter spin-out company, Isca Diagnostics Limited.

Submitting Institution

University of Exeter

Unit of Assessment

Biological Sciences

Summary Impact Type

Technological

Research Subject Area(s)

Medical and Health Sciences: Clinical Sciences, Immunology, Oncology and Carcinogenesis

Discovery and development of thalidomide analogues for treatment of myeloma and other cancers

Summary of the 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.

Submitting Institution

St George's, University of London

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Clinical Sciences, Oncology and Carcinogenesis, Pharmacology and Pharmaceutical Sciences

Improving treatment guidelines, life expectancy and access to life insurance for HIV positive people

Summary of the impact

In 2011, 34 million people worldwide were living with, and 1.7 million died from, HIV/AIDS. Since 2002, HIV-positive people have benefited from research by the Antiretroviral Therapy Cohort Collaboration (ART-CC) based at University of Bristol (UoB). Research on the timing of ART led to updated international HIV treatment guidelines that recommended starting treatment earlier. Research on life expectancy highlighted the benefits to patients of earlier ART, and was used by policy makers, clinicians and patient groups to promote earlier treatment. Patients are now starting treatment earlier resulting in increased life expectancy. Insurance companies changed their criteria for providing life insurance, influenced by ART-CC.

Submitting Institution

University of Bristol

Unit of Assessment

Public Health, Health Services and Primary Care

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Public Health and Health Services

Global health impact and economic impact from the development of FreeliteĀ®

Summary of the impact

Research conducted by Professor Jo Bradwell at the University of Birmingham provided the basis of the commercially available diagnostic test Freelite®, which quantifies free immunoglobulin light chains in serum and was the first and only assay for the diagnosis and monitoring of Multiple Myeloma (MM). MM is a cancer of immunoglobulin producing plasma cells in the bone marrow. Freelite® has markedly improved the diagnosis and management of MM, is helpful in the diagnosis of all B cell lymphoid neoplasias and provides prognostic information for premalignant conditions present in over 3% of people over 50 years of age. Freelite was commercialised by the University of Birmingham spinout company, the Binding Site, which has achieved worldwide sales, with over 360,000 tests being sold per month in 90 countries and an ongoing 25% annual growth in sales. The company provides annual revenue of £55m and employment for 620 people in the UK and abroad. An improved second generation of tests has been developed by Professor Mark Drayson at the University of Birmingham, which has been commercialised by a second University spinout company Serascience, which started marketing a point of care free light chain diagnostic test worldwide in April 2013.

Submitting Institution

University of Birmingham

Unit of Assessment

Clinical Medicine

Summary Impact Type

Technological

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Immunology, Oncology and Carcinogenesis

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