Earning their stripes – Zebrafish lead the way to learning more about MND

Zebrafish are increasingly becoming the organism of choice to study both early development and disease. But why are zebrafish important to MND research and can we really learn anything from a fish?

Shall I compare thee to a zebrafish?
Amazingly, we share many of our genes with our finned-friend the zebrafish which means that we really can compare what happens in zebrafish with what happens in humans.

With transparent embryos, zebrafish offer a unique view into the developing fish which means that researchers can study their neurones under a microscope – a feat that is not possible in humans or other mammals. We can also learn about how the disease progresses in fish by measuring their muscle strength by the amount they move, and by measuring their progress swimming against a current in a tube. 

Unlike us, zebrafish are also able to regenerate motor neurones if they become damaged. Interestingly – it is not that we do not have this capacity; we have extra signals that tell our motor neurones not to regenerate.

Zebrafish can therefore be used in MND research to gain a greater understanding of the processes that govern both the degeneration and regeneration of motor neurones to develop new and better treatments.

In the past 30 years, the number of scientific articles published about zebrafish has increased 465 fold. Not only does this show the increased use of this model, but also represents our collective increase in understanding more about human diseases and human development.

We’re fishing our way to a world free of MND
One of our newest projects, set to begin later this year, will be using a new zebrafish model of MND to screen over 2,000 potential new drugs to test for their effectiveness. This work will be carried out at the University of Sheffield by Dr Tennore Ramesh and Prof Pam Shaw.

This project will join the ranks of many other MND Association funded projects that are developing new models of MND to learn more about the causes of MND so that we can be in a better position to develop treatments.

We have also recently supported the development of new guidelines for the use of models in MND research in order to improve our confidence in pre-clinical (laboratory) studies and hopefully the success rate of MND clinical trials.

Zebrafish will not be able to provide us with all of the answers as to what causes the disease, or how we can treat it. But, when used in combination with a number of other exciting disease models, including chick embryos, flies and mice, we can push MND research to a new and exciting level.

One week on – Reflections on my first experience of the International Symposium on ALS/MND

Our recent blog articles describe lots of fascinating science and the progress in the care and treatment of MND/ALS that was presented at the symposium.  Personally, another really positive aspect was the opportunity to meet some of the researchers face-to-face. This included several senior scientists and clinicians whose work we support, some of whom gave lectures or chaired sessions. The symposium also gave presentation opportunities to PhD students and post-doctoral scientists, some of whom were attending their first International Symposium. We invited several from the UK to an ‘ice-breaker’ social on the Friday evening before the main lecture sessions began. Not all were able to attend, but a good group gathered with us, getting to know each other, and we met others later as they presented their posters. 

Sheffield University was well represented, including current grantees Emily Goodall and Clare Wood-Allum who both presented posters. Newer to ALS research was Guiseppe (‘Bepe’) Battaglia part of a cross-disciplinary group of collaborators who call themselves ViNCeNS for ‘Virus-like Nanoparticles for targeting the Central Nervous System’ with a website at www.vincens.group.shef.ac.uk/index.htm.

‘Fishing’ for new animal models of MND

Two others at our ‘ice-breaker’ gave lectures during the Saturday session on ‘Emerging Disease Models’.   Marc Da Costa (also from Sheffield) described some outcomes of his PhD project developing a new zebrafish with a mutated SOD1 gene.  Zebrafish are popular models for neurological conditions (there was a second presentation from an US-based group), as the fish embryos are transparent, so their neurones can be studied easily under the microscope.  Their muscular strength can be judged by the amount they move (studied by automated analysis of video) or by their progress swimming against a ‘current’ in a tube.  Marc studies the differences between fish with normal or mutant SOD1.  The latter have more difficulty swimming, and are more vulnerable to stress (for example, added toxic chemicals).  Marc can test the effects of potential drugs on the stressed fish, and has already seen some promising results.

Looking in a ‘library’ for MND mice

Another new animal model was presented by Peter Joyce (MND Association funded, based at the Medical Research Council Laboratories near Oxford).  His mouse strain carries a mutation (mistake) in its native (mouse) SOD1 gene, matching one recently reported from a human family with ALS.  This is different from the more established SOD1 mouse model, in which the MND-like symptoms develop as a result of multiple copies of an added human mutant gene.  Peter is studying the timescale in which muscle problems develop, relating these to changes in the neurones.  The MRC has a huge ‘library’ of mouse mutations available, so Peter will be investigating if others match mutations reported in different ALS families, possibly looking for collaborators to work on these.

Presenting the impact of healthcare decisions

A completely different type of research was presented as posters by two researchers working with Carolyn Young at the University of Liverpool.  Hikari Ando has been studying the reasons why some people with MND decide not to accept the offer of non-invasive ventilation (NIV), and the extent to it is actually used by at home.  Chris Gibbons’ work covered the assessment of quality of life for people with MND, particularly the role of fatigue and depression. 

Final thoughts

It was particularly inspiring to meet so many UK-based researchers, filling all of us from the MND Association with more incurable optimism.  Of course we also met many other people too – the attendees, many of whom collaborate internationally, came from more than 30 countries.