Tropical zebrafish have helped researchers at the University of Sheffield pave the way for the discovery of new anti-inflammatory drugs to treat illnesses such as chronic obstructive pulmonary disease (COPD) and asthma.

The research team led by Dr Stephen Renshaw, Senior Clinical Lecturer in the Clinical Academic Unit of Respiratory Medicine at the University, has set-up a system for drug screening after finding important parallels between inflammation in the 3mm long larval fish (a similar stage to a tadpole) and in humans - proof that the zebrafish can be used to find anti-inflammatory drugs.

The team's work, which was published online this week in the Journal of Leukocyte Biology, focuses on the behaviour of a key cell in inflammation called the neutrophil, using a model of neutrophil behaviour in the larvae of zebrafish. This unique model is the only way to visualise these cells during inflammation, and given the small size of zebrafish, makes drug screens a practical prospect using this approach.

After discovering parallels between inflammation in the fish and inflammation in humans, Dr Renshaw's team looked at a range of known anti-inflammatory drugs used on humans. They were able to show that a number of these drugs worked in zebrafish, thereby establishing that zebrafish could be used to identify new potential therapeutics for humans.

The study, which was conducted in the University's MRC Centre for Developmental and Biomedical Genetics, is the first published proof of principle work to show that zebrafish models can be used to find anti-inflammatory drugs. It also demonstrates the power of zebrafish drug screening recently established in the University with a £1.5million translational pump-priming grant from the MRC.

It is hoped the published research will be the first of many such projects and will lead to exciting new drugs for treating patients with inflammatory diseases, including respiratory illnesses.

Dr Stephen Renshaw, of the University of Sheffield's Department of Infection and Immunity in the Medical School, said: "I am very excited by the potential of zebrafish to find new drugs for human inflammatory diseases as we are always looking for better ways to treat the large numbers of patients with respiratory disease in Sheffield, the UK and across the globe.

"This success is only the first of a range of zebrafish drug screens, which I am hopeful will provide real benefits to health in the coming years."

Notes

The MRC Centre at Sheffield is one of fifteen long-term partnerships between the MRC and UK universities. They are intended to help universities to develop and sustain centres of scientific excellence with clear strategic direction in areas of importance to UK medical research.

The Centre for Developmental and Biomedical Genetics (cdbg) at the University of Sheffield is internationally recognised as a leading centre for biomedical research. Originally founded in 1997 as the Centre for Developmental Genetics, the Centre was renamed in 2004 to reflect its growing emphasis on models of human development and disease. In 2007 it was awarded full MRC centre status.

Core funding for the Centre is provided by the Medical Research Council (MRC) while individual research projects are supported by a number of agencies including the MRC, the BBSRC, The Wellcome Trust, Cancer Research U.K as well as the European Union 6th framework Programme.

Source
University of Sheffield