Nanoparticle delivery of conventional and novel drugs for tuberculosis

2015 Interdisciplinary Prize Winner

Prof Sir Mark Welland, Prof Andres Floto & Dr Mark Schiebler, University of Cambridge

Tuberculosis (TB) is a bacterial infection that affects the lungs, causing a chronic cough, fever and weight loss.  Treatment of TB has been hampered due antibiotic resistance, and poor compliance due to the long, complicated treatment regimes, highlighting the need for new drug delivery strategies.  This innovative project aims to revolutionise the delivery of TB treatments, by combining advances in material science and nanomedicine to develop a single formulation.  By incorporating the drugs into the structure of the nanoparticle, the researchers hope to deliver combination therapies, directly to infected cells, leading to ‘simpler, safer and more effective treatment’ for TB.  This strategy could also be used for other diseases that require a combination of drugs.

How effectively does the cellular immune system of infants and young children respond to HIV-1 infection?

Prof Sarah Rowland-Jones, University of Oxford

Mother to child transmission is an important cause of new HIV-1 infection worldwide, despite increased implementation of prevention strategies. Infants that have been infected with HIV from their mothers during pregnancy, birth or breast feeding typically have very little control of HIV levels without the aid of anti-retroviral therapy. This leads to a much higher risk of progression to AIDS and death. The aim of this study is to assess the immune response in infants with HIV, with a focus on killer T-cells. These are immune cells that are responsible for eliminating HIV-infected cells and suppress the replication of the virus. The researchers will use samples collected from mothers and from infants at different times after birth as part of the ‘CTLs and Prevention of HIV-1 Transmission Study’ carried out in Nairobi, Kenya. These will be used to investigate more about the killer T-cell response to HIV infection, and look at genetic changes in T-cells after HIV infection.  This will provide a greater understanding of how the immune system matures in the face of HIV infection. The researchers believe this study will also provide new and crucial information that should help in designing new vaccines and immune based therapies to prevent and treat HIV infection in children in the future.

Identifying causes of childhood inflammatory disease

Professor Paul Brogan, UCL & Great Ormond Street Hospital

The aim of this research, led by Professor Paul Brogan is to set up a new gene discovery service for children with inflammatory diseases such as arthritis. Around 1/1000 children suffer from arthritis, but in many cases the cause is unknown.  Understanding the genetic changes that cause a disease improves the possibility of developing a treatment. At present, only simple testing is available on the NHS for diagnosing already known disease causing genes. In this study Professor Brogan’s team are trying to identify new genes that cause inflammatory diseases during childhood, and develop a single test that can screen over 150 genes associated with inflammation.

Prolonging transplanted organ survival using a novel immune based therapy

Dr Lesley Smyth, King’s College London

Transplantation is the treatment of choice for failing organs such as the heart, kidney or lungs.  Success, and long-term survival of a new organ is limited by the immune system; recipients often require immunosuppressant drugs, which have serious side effects, and can damage the organ. Immune cells have different functions; some fight infection, while others (regulatory T-cells) can prevent unwanted immune responses against proteins that are expressed naturally by our own body.  Previous studies have shown that increasing the number of regulatory T-cells can prevent organ rejection in pre-clinical models.  However, these cells are vulnerable to factors that could prevent their action.  Further study has shown that these cells release vesicles which can stop an immune response, although how they do this is unclear.  This study aims to investigate if these vesicles could have potential in the prevention of organ rejection, by understanding how they contribute to the immune response, and what they target.  If successful, this work could help to improve the long term survival of a transplanted organ, as well as reducing the use of drugs associated with serious side effects.  This would improve patient quality of life, as well as reducing transplant lists.

A new treatment for severe lung infection in infants and the elderly

Dr Fiona Culley, Imperial College London

Respiratory syncytial virus (RSV) infection is the most common cause of severe lung infections, and severe RSV infection in infants may permanently damage the lungs and increase the risk of developing asthma in childhood. RSV infection can also cause very severe illness in the elderly, and may often be mistaken for the flu in this age group. There are currently no good, affordable treatments for RSV and no vaccine. Collaborators at the University of Sheffield have previously developed a new anti-viral treatment and have shown that when applied to lung cells in the laboratory it can reduce infection and inflammation caused by the common cold virus. By studying the ability of the treatment to prevent infection and production of new virus particles, and reduce inflammation in human lung cells, this project aims to determine its potential as a treatment for RSV.



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