Closing the door on toxic proteins – new clues in understanding a genetic form of MND

The defects in the C9orf72 gene are known to cause motor neurone disease, but researchers don’t understand why. Defective copies of this gene are passed down in some families affected by the rare, inherited form of MND. This week MND Association grantees Drs Guillaume Hautbergue, Lydia Castelli and colleagues, based at the Sheffield Institute of Translational Neuroscience have published their research study providing some important clues about the toxicity of C9orf72. Their research is published in the prestigious journal Nature Communications. Continue reading

Pretty ‘fly’ for a fruit fly

A fruit fly

Dr Frank Hirth is one of the world’s leading fruit fly MND researchers. Based at the Institute of Psychiatry, Psychology and Neuroscience at King’s College London, he has been working on an Association-funded project developing a C9orf72 fruit fly model of MND. Here we mark the end of this project, and report on what the researchers have achieved.

Background

In September 2011, an international collaboration, co-funded by the Association, had discovered a genetic mistake within the C9orf72 gene that was found to cause almost 40% of cases of inherited MND. Continue reading

Flying towards understanding: MND, TDP43, flies and a competition

Dr Frank Hirth King's College London

Dr Frank Hirth, King’s College London

The MND Association has funded a number of research projects in the laboratory of Dr Frank Hirth at the Institute of Psychiatry, King’s College London. His area of expertise is in using fruit flies to understand how motor neurones die in MND.

There is an opportunity to read a summary of some of his work through an online competition. The article is called ‘The TBPH gene – do neurodegenerative disease have a fly in the ointment’ and it is has been shortlisted forThe People’s Choice award , as part of the Access to Understanding competition.

Please go online, read the article, ‘like it’ and add any comments you’d like to, until a deadline of 12 noon on 24 March.

A background (but hopefully not a spoiler!) to this summary and the competition is given below:

Continue reading

Come fly with me

The Fly

The Fly. Courtesy of MND Association funded researcher Dr Frank Hirth, based at King's College London

Although millions of years of evolution separate humans from insects, a tiny fruit fly called Drosophila melanogaster has been one of the most extensively studied organisms for more than a century, leading to many advances in research. But why are flies so useful? And can we really learn anything from them?

Why fly?

It is easy to see that this fly has advantages in the laboratory. They are very small and easy to keep, but still large enough to study in detail with relatively simple microscopes. They breed easily from 10 days old, producing many genetically identical offspring from each mating. This makes it easy to study several generations over a matter of weeks.

Simple yet sophisticated

Although considered a simple species, the fly is actually quite sophisticated, with structures that are equivalent to organs such as the heart, kidneys and gut.  The brain and nervous system are considered particularly complex, making the fly valuable for the study of neurodegenerative diseases.

Genetically the fruit fly is also much simpler than a human – it has approximately half the number of genes that we do. But it’s not the number of genes you have that counts; it’s what you do with them!

Luckily, about three-quarters of the genes implicated in human disease have a related gene in the fly, with a high level of similarity between the two. Many methods and techniques have been developed, so researchers can switch the fly’s genes on and off at various points in its life-cycle, or in different parts of the body, and then observe the consequences.

MND fly research

Between 2004 and 2009, only about four scientific papers per year described studies using these fruit flies for MND research. In conjunction with the recent upsurge in genetic discoveries related to MND, there has been a rapid increase to twelve publications in 2010, and a further seven already in 2011.

The MND Association is a leader in funding and promoting cutting edge research and we are currently funding two PhD studentships making extensive use of the fruit fly. You can find out more about these projects on our website:

Understanding disease mechanisms of MND in the fruit fly

How does faulty TDP-43 affect MND in fruit flies?

Learning to fly toward drug discovery

There is considerable interest in using the fly to test potential drugs for MND, as there has been some success in this approach in other conditions.  Like the zebrafish model many more substances can be tested than would be possible with a mouse model, and the results may tell scientists more than a cell-based screen. However, this is not yet a routine approach to drug discovery – historically fruit flies have not been used in this way by pharmaceutical companies. It remains to be seen whether any promising compounds identified using fly models will actually progress to being drugs for the treatment of human diseases.    

For such an approach to be useful for MND, there needs to be a reliable and relevant fly model. Recently published work has been focussed on exploring the role of proteins known to be involved in MND such as TDP-43 and FUS. When they publish their work, researchers often hint that their models will be useful in the development of new treatments, even if this was not their main aim.

The use of the fly to discover new medicines may still be some way off, but we can be sure that the tiny fruit fly is already contributing to research in a very big way.