New genetic marker discovered for motor neurone disease

The quest for genetic markers to explain the complexities of motor neurone disease (MND) has moved ahead via a study led by researchers at Western Australia’s Perron Institute and Murdoch University.

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

This is the first genetic association of its kind to be published and forms the basis for a filed international patent. Results indicate that the variation is a risk factor and may affect the progression of the disease in some patients.

Motor neurone disease is a neurodegenerative disorder that results in progressive paralysis, with patients usually succumbing in one to five years after diagnosis. An estimated five to ten percent of cases are familial, but most are sporadic.

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

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

“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.

“A stratified approach could provide greater precision, informing the development of more targeted therapies for ALS patients. Improved cost effectiveness of clinical trials is another benefit,” Professor Akkari said.

Lead investigator for the study, Frances Theunissen, is a research assistant and PhD candidate (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.”

The scientific article, Novel STMN2 Variant Linked to Amyotrophic Lateral Sclerosis Risk and Clinical Phenotype, was published in Frontiers in Aging Neuroscience, a leading journal in its field.

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

It was funded by the Perron Institute, the Giumelli Foundation, Ian Potter Foundation, Racing for MNDi Foundation and the Pierce Armstrong Foundation.