Northcott Neuroscience Laboratory Projects

Motor Neuron Disease (MND) and Disorders

G Nicholson

The motor neurons are nerves that extend from the brain to the muscles and provide the stimulus through which we move, breathe, eat and drink. The motor neuron diseases (MND) are a group of related neurodegenerative diseases that cause the progressive death of motor neurons. These diseases range from slowly progressive, non-fatal forms to the rapidly progressive fatal disorder amyotrophic lateral sclerosis (ALS). ALS typically leads to death within 3 to 5 years of first symptoms. ALS causes progressive paralysis and the cause of death is usually respiratory failure.

There are no specific diagnostic tests for MND and treatment is extremely limited. The only known causes of MND are mutations in particular genes that lead to death of motor neurons. The known MND genes only account for about 2% of all cases. We are working to understand the biological basis of MND through identification and analysis of defective genes that cause the death of motor neurons. This understanding is a prerequisite to effective diagnosis, treatment and prevention of MND.

The laboratory has been at the forefront of MND discoveries for many years. After demonstrating that MND can be caused by any of a number of genes with mutations we showed that TDP43 mutation variants cause MND. Protein expressed by this gene is found in all dying nerves in MND. This has led to world attention to find ways to correct this. Our work is continuing as a research collaboration with Macquarie University’s motor neurone research group, where Professor Nicholson has mentored both the Genetics group and the Zebra fish group. At the ANZAC Northcott laboratory we are continuing to find new gene variants causing non-fatal forms of motor neurone disorders in families attending our neurogenetic clinic by using next generation DNA sequencing. Genes causing motor neurone disorders can sometimes be severe and life threatening and may play a role in the fatal forms of MND.