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.

Changing the way we treat skin cancer

Researchers at the Illawarra Health and Medical Research Institute are leading a multi-institutional research project to better understand and treat squamous cell carcinoma (SCC) of the skin, one of the most common skin cancers in Australia.

Thanks to three-year funding from the National Health and Medical Research Council, IHMRI’s Senior Professor Marie Ranson and Associate Professor Bruce Ashford, who are leading the project, are investigating molecular changes of the cancer to determine what causes it to spread.

“SCC of the skin is so common amongst Australians, but we still don’t know why some tumours spread to nearby lymph nodes and why others do not,” Senior Professor Ranson said.

“Our aim is to decipher the molecular changes that distinguish those SCCs that are likely to spread so that clinicians can identify and treat these patients early.”

Senior Professor Marie Ranson

A better prognosis, more targeted treatments

The project aims to achieve better prognosis and more targeted treatments for one of Australia’s most common cancers and major healthcare burdens.

Patients with aggressive variants of cutaneous SCC often present late, when the cancer has already spread through lymphatics to nodes in the neck.

“When patients present at such a late stage, we have to treat with both radical surgery and high dose radiotherapy. Even then, the chances of surviving beyond five years are only about 50%,” A/Professor Ashford explained.

“We want to be able to identify whether there are early markers that distinguish whether we can avoid unnecessary surgery, or whether we should use even more aggressive treatment.”

Associate Professor Bruce Ashford

Understanding the genetic landscape

Senior Professor Ranson, A/Professor Ashford and the IHMRI team are unravelling the genetic landscape of SCC through the process of whole genome sequencing. Through this process, researchers can see if there is a signature within these tumours that can help predict which ones will spread.

“If we find a signature, it will enable clinicians to more accurately identify at-risk patients to diagnose and treat metastatic SCC early. We have so far completed whole genome sequencing on 33 patient specimens and are completing RNA sequencing of these tumours,” Senior Professor Ranson explained.

The tumour samples are collected from surgery at both Wollongong Hospital and the Chris O’Brien Lifehouse in Sydney. Whole genome sequencing works by comparing cancer cells to normal cells to check for mutations in the DNA. If researchers can find a common pattern of mutation within the cancers, it will help identify which tumours will spread.

“Over three years we hope to examine between 60 and 80 patient specimens. This grant also helps fund the employment of bioinformaticians to help us understand the complex nature of DNA variation in this deadly disease,” said Senior Professor Ranson.

The project is a collaboration with partners, Associate Professor Ruta Gupta from Royal Prince Alfred Hospital, and Professor Narayanan Gopalakrishna Iyer from the National Cancer Centre in Singapore.