Using zebrafish to increase our understanding of motor neurone disease

In people with MND, the motor neurones which normally control voluntary muscle movements like speaking, walking and swallowing begin to weaken and gradually waste away.

Although rare, affecting two in 100,000 people in the UK at any one time, around one in 300 people will develop MND at some point in their lives. MND has a significant impact on people’s lives and there is no cure. Life expectancy for around half of those with the condition is just three years from the start of symptoms – making new research vital.

Thanks to a gift in Will from Irene Griffiths, who wanted to help UK scientists tackle this devastating disease, we have been able to support some of the brightest and best MND researchers in the country – including Dr Bradley Smith from King’s College London.

Bradley uses zebrafish models of MND to pinpoint biological mechanisms of potentially harmful genetic mutations in new MND genes. His research has found that the most common genetic mutation in a new gene called Annexin A11, when modelled in zebrafish embryos, slowed down the movement of neurones in the brain. He also discovered that ‘switching off’ the zebrafish equivalent of this gene resulted in abnormal motor neurone formation, such as reduced branching of neurones. Bradley’s research highlighted that this gene is important for normal neuronal function, and next he will assess these results in mouse models.

“The fellowship has been immensely valuable to my research,” says Bradley. “It has provided two key opportunities, firstly to address a fundamental issue in MND genetics, which is the evaluation of new gene candidates to assess if mutations are detrimental to motor neurone function.

“Secondly, it adds highly specialised new skills to my professional toolkit and will provide a stepping-stone to being an independent researcher in the MND field.

“Through our research to date, we have identified a potential disease mechanism, and we can now link this gene into several well-known MND pathways, helping to build a better understanding of common denominators for the disease.”

Bradley added: “The fellowship has also contributed to my own development by enabling me to communicate my research, present at MND patient forums, and train emerging scientists. I have also been awarded Lectureship at King’s College London, off the back of my fellowship.”