Fish can help solve mystery of debilitating motor neurone disease

Research involving zebrafish can provide vital breakthroughs in tackling the degenerative motor neuron disease (MND) which affects nerve cells sending messages to the brain. A person with MND experiences weakening of muscles and soon loses ability to move or speak.

Scientists from the University of Sheffield have created zebrafish that carry the complex genetic change known to cause the most common genetic form of motor neurone disease. This will speed up research and experimental drug trials to combat the disease. Scientists searching for causes of the disease and working on experimental drugs earlier conducted trials on fruit flies and mice models, which had its limitations as the brains of humans and fruit flies were vastly different and there were cost implications of using mice models, a release from the University of Sheffield said.

Now, researchers from the university’s Institute of Translational Neuroscience (SITraN) have created what’s been called the “complex aspects of human C9- amyotrophic lateral sclerosis (ALS)/ frontotemporal dementia (FTD) pathobiology in zebrafish models.”

The study published in the journal Acta Neuropathologica Communications was funded by the MND Association.

This breakthrough will be helpful for researchers to study the devastating disorder with affects the nerves or motor neurons in the brain and spinal cord that “tell muscles what to do,” says the release. When signals don’t reach muscles these weaken and eventually waste away, affecting a person’s ability to walk, talk eat or breathe.

Currently there is no cure for the disease.

The most common known genetic cause of MND and FTD is an abnormality of a gene. The C9orf72 gene has countless repetitions of the GGGGCC sequence in MND patients.

Complex genetic and environmental interactions not well understood also cause MND.

“Using zebrafish models for MND research means that we can accelerate studies and our understanding of the devastating disease and other neurological conditions,” says Dr Tennore Ramesh, from SITraN at the University of Sheffield. Zebrafish, a freshwater fish belonging to the minnow family of the order Cypriniformes is a popular aquarium fish and native to the Himalayan region. As it’s transparent you can record results of studies quickly and easily and research is less invasive, Dr Ramesh adds.

Testing 1,000 drugs on mice models would take more than 10 years, however trialling 1,000 drugs on zebrafish would take only a couple of months. “This will enable us to accelerate research into clinical trials in humans quicker than ever before,” he says.

The four year project, which was led by Dr Ramesh in collaboration with leading researchers from SITraN including Professor Dame Pamela Shaw, Vice-President and Head of the Faculty of Medicine, Dentisry and Health at the University of Sheffield, is published in the journal Acta Neuropathologica Communications. The study was funded by the MND Association.