Motor neurone disease genetic marker discovery

A genetic variant linked to the most common form of motor neurone disease, which holds potential as a genetic marker to better treat the neurological disease, has been discovered by researchers at the Perron Institute and Murdoch University.

The study represents a step forward in the quest to find new genetic markers to understand and advance new approaches to treat the complexities of motor neurone disease (MND).

MND is a neurodegenerative disease resulting in progressive paralysis. An estimated five to ten percent of cases are familial (hereditary), but most are sporadic.

Study marks first genetic association of its kind in MND research to be published

The collaborative research investigated the Stathmin-2 gene, which is necessary for neuron growth and regeneration. The team uncovered a structural variant within this gene that is linked to sporadic amyotrophic lateral sclerosis (ALS), the most common form of MND.

Results indicate that the variation is a risk factor and may affect the progression of the disease in some patients.

Professor Anthony Akkari, senior author of the study who heads the Motor Neurone Disease Genetics and Therapeutics Research team at the Perron Institute and Centre for Molecular Medicine and Innovative Therapeutics at Murdoch University explained.

“Identifying variations in genetic makeup is a key element in improving approaches to preventing, diagnosing and treating diseases such as MND.

“Overall, in this area of unmet need, the aim is to discover what therapies would work best for specific patient groups. Our research is aimed at filling in genetic pieces of the puzzle.

“As well as giving us a better understanding of disease mechanism, knowledge of this variant could improve outcomes of clinical trials. Grouping participants by this genetic marker would enable researchers to investigate whether the sub-group responds differently to a particular therapy.”

Frankie Theunissen and Prof Anthony Akkari at Perron Institute
Lead researchers Frankie Theunissen and Prof Anthony Akkari at the Perron Institute

Frances Theunissen was lead investigator of the study, a research assistant and PhD candidate at the Perron Institute and Murdoch University.

“This newly discovered genetic variant has the potential to be a disease marker and tool for cohort enrichment in future MND clinical trials and this strategy should become standard practice,” she said.

“It’s a step towards developing new, personalised treatments for motor neurone disease.”

Frances Theunissen

The study was published in the journal Frontiers in Aging Neuroscience.

The collaborative study involved renowned local researchers and international collaborators, including Professors Don Cleveland, John Ravits and Dr Ze’ev Melamed (University of California, San Diego), Professor Richard Bedlack (Duke University, North Carolina) and Professor Alan Mackay Sim (Griffith University, Queensland).

The research was made possible thanks to funding from the Perron Institute, the Giumelli Foundation, Ian Potter Foundation, Racing for MNDi Foundation and the Pierce Armstrong Foundation.