The importance of discovering genetic markers and how their use in clinical trials could assist in identifying motor neurone disease patient sub-groups was the theme of an article published recently in the journal BMC Medicine.    

Amyotrophic lateral sclerosis (ALS) is the most common form of MND, a severely life-shortening neurodegenerative disease with few treatments.   

First author for the expert opinion article ‘Short structural variants as informative genetic markers for ALS disease risk and progression’ was PhD candidate Frances Theunissen from the Motor Neurone Disease Genetics and Therapeutics Research group at the Perron Institute and the Centre for Molecular Medicine and Innovative Therapeutics at Murdoch University.  

“We discuss how the application of genetic markers to clinical trials could help to better identify ALS patient sub-groups that may progress in a similar way,” she said.  

“This paper highlights different examples of novel short structural genetic variations our team has discovered that are associated with ALS disease risk or clinical phenotype. 

“It builds on our 2020 publication suggesting genetic regions may hold the key to understanding the variability in ALS patient disease risk and progression.   

“The publication discusses methods and ideas for using the genetic markers we’ve discovered for ALS to improve the outcomes of clinical trials. It outlines our structural variant discovery platform, a tool to identify which patients are more likely to respond to particular ALS therapies to improve future testing.”   

The senior author is Professor Anthony Akkari, who heads the MND Genetics and Therapeutics Research group.   

“Various disease markers could prove critical to improving the chances of clinical trial success,” he said.   

“The markers we’ve identified could also help with patient prognosis and provide information on disease progression and response to drugs.    

“We also provide evidence of three of our discovered genetic markers, two of which deliver the first report linking the genes SCAF4 and STMN2 to ALS – an important finding for us. 

“We’re driving these discoveries forward as fast as we can through Black Swan Pharmaceuticals, a United States-based biotech company in partnership with Perron Institute and Murdoch University.”  

The other publication authors are Associate Professor Ryan Anderton (The University of Notre Dame) and Dr Loren Flynn, a postdoctoral scientist in the MND Genetics and Therapeutics Research group.  

The team’s next step is to continue the development of the structural variant analysis platform. This is partly supported by a $250,000 FightMND grant received last year titled ‘Identification of Novel Structural Variations in ALS genes to Improve Outcomes of Clinical Trials’.   


Pictured L-R: Frances Theunissen and Prof Anthony Akkari.