Zebrafish and fruit flies
Genetic modelling using zebrafish and fruit flies at the University of Sheffield is reducing the time it takes to bring new drugs to market by identifying how existing drugs can be used in novel areas – giving hope to patients suffering from inherited diseases that treatments will be found sooner rather than later.
Already researchers at the University’s MRC (Medical Research Council) Centre for Developmental and Biomedical Genetics (CDBG) have made a significant breakthrough in the treatment of Parkinson’s disease by screening fruit flies with a drug usually used to depress the immune system in transplant patients.
Lead researcher Dr Alex Whitworth said: ‘We were studying how two genes known to cause rare inherited forms of Parkinson’s (the PINK1 and Parkin genes) affect nerve cells in the brains of fruit flies.
‘Fruit flies with either of these mutations have damaged dopamineproducing nerve cells and problems with mobility similar to Parkinson’s. But we found that giving the fruit flies a drug called Rapamycin – usually used to prevent the rejection of transplanted organs – could protect the flies against the effects of mutations.’
Crucially, this study identified a key pathway inside nerve cells that can be stimulated to protect the cells affected in Parkinson’s.
‘It’s early days yet, and there’s a great deal of work to be done before we will know if these findings can be applied to all forms of Parkinson’s. But the discovery of this pathway reveals the exciting potential that genes hold for understanding Parkinson’s and developing drugs that could slow or even stop the progressive loss of nerve cells in the brain.’
Dr Kieran Breen, director of research and development with the Parkinson’sDisease Society, the main backers of the study, said: ‘This is an exciting new development in the search for new and better treatments for Parkinson’s. The discovery of this pathway may be the key to developing new drugs that could slow or even stop the progressive loss of nerve cells in the brain.’
Professor Philip Ingham, who set up the MRC Centre some eight years ago, says he was determined from the outset that the CDBG would be committed to collaboration and use focused and directed research to produce real world treatments for diseases.
‘When we first thought about setting up this centre I talked to a number of clinicians at the Medical School to see if they were interested in working with us on modeling diseases using the zebrafish,’ he said. ‘I found that we were pushing at an open door.’
Collaboration with the Medical School is deepening the Centre’s interest in neuro-degenerative diseases as well as neuro-behavioural disorders using zebrafish as a non-mammalian model. The neuroanatomy of the fish brain is surprisingly similar to that of human and fish show a variety of behaviours analogous to human disorders such as anxiety, aggression and depression. Other research teams at the Centre are using zebrafish to study a diverse range of diseases, from chronic inflammation to bone tumours, as well as in a search for a cure for blocked arteries.
‘We are pioneering this approach in the UK,’ said Professor Ingham, who acknowledged that there is still some scepticism within the biomedical science community as to the validity of using fish as a model for human. ‘One of the great things about the fish is the ease with which they can be exposed to different agents, which means we can very rapidly screen many hundreds of existing drugs to uncover their previously unknown effects’
‘This has the potential to save millions of dollars or pounds that are needed for the conventional process of developing new drugs de novo. It saves valuable time in lengthy clinical trials. It means you don’t have to do phase one trials because these have already been done – the drugs are already in use and have been approved. This is very important benefit to the patient, since it greatly reduces the time it takes to get a drug approved.’