Major Boost: MND Research Centre Secures $1.5 Million in Funding

The funding includes US$750,000 (about AU$1.125 million) from the US Department of Defense’s Congressionally Directed Medical Research Programs and four grants from MND Research Australia, each worth $100,000.

Also known as amyotrophic lateral sclerosis (ALS), MND causes the progressive loss of the neurones that allow the brain and spine to communicate with the muscles. It is currently untreatable, and most patients die within two to five years of diagnosis.

A team led by Dr Albert Lee has received their funding as part of the Department of Defense’s 2023 Amyotrophic Lateral Sclerosis Research Program Therapeutic Idea Award – Biomarker Option. One of the identified causes of MND is the abnormal build-up of the protein TDP-43 inside the motor neurones of the brain and spinal cord. Dr Lee’s project aims to develop a gene therapy that will cause the over-expression of the protective molecule that clears TDP-43. The team hopes the gene therapy could prove to be an effective treatment for both familial and sporadic MND.

Project leaders: (Clockwise from top left) Dr Albert Lee, Dr Cindy Maurel, Associate Professor Marco Morsch, Professor Yuling Wang, Dr Sayanthooran Saravanabavan, and Dr Shu Yang. 

Projects led by Associate Professor Marco Morsch, Dr Cindy Maurel, Professor Yuling Wang and Dr Shu Yang, and Dr Sayanthooran Saravanabavan were funded with MND Research Australia’s Innovator Grants.

A project led by Associate Professor Marco Morsch and titled, ‘Targeting the nucleus: Is TDP-43 supplementation in the nucleus enough to delay disease progression?’, received the Doug Parry MND Research Grant. The project will investigate the primary cause of the aggregation of TDP-43 and how it can be prevented. It will test whether nuclear supplementation of TDP-43 is sufficient to delay disease progression, providing preclinical validation of a novel approach.

A project led by Dr Cindy Maurel, ‘Probing molecular drivers of TDP-43 phase transition: the influence of lysine modifications’, received the Bruce Catto MND Research Grant. The project aims to provide crucial new knowledge of the mechanisms driving TDP-43 aggregation. The team developed and will apply an innovative set of techniques to assess the role of specific modifications that have emerged to be implicated in such accumulation of TDP-43 in a living nerve cell. They will provide a comprehensive evaluation of how modifications of lysines can influence pathology.

Professor Yuling Wang and Dr Shu Yang were funded under the Daniel McLoone MND Research Grant for their project, ‘Investigating the role of extracellular vesicles (EVs) membrane’. All cells release tiny particles called extracellular vesicles (EVs). They are the ‘messengers’ of the cell and can deliver many important information molecules to help a specific group of cells communicate with one another. Because of this unique function, EVs can be used to help understand how harmful MND proteins are transmitted among cells and to use them for diagnosis and drug delivery. The study aims to compare EVs released from healthy and MND-affected nerve cells to understand how harmful proteins are passed from one motor neurone to another. With this knowledge, the team hopes to understand how MND progresses and design strategies to tackle this process.

‘Examining the pathogenic roles of circular RNAs in genomic instability in ALS’, a project led by Dr Sayanthooran Saravanabavan, received the Run MND NSW Research Grant. Genomic instability in motor neurones is fundamental to the origin and repercussions of MND pathology and therefore an ideal target for preventative interventions. A paradigm shift in the past decade revealed that non‑coding RNAs are essential for safeguarding the genome’s integrity. MND-associated proteins are central players in RNA metabolism, suggesting a link between genomic instability in MND and the realm of RNA. This project will examine the role of circular non-coding RNA in MND and advance insights into its causes, proposing both strategies to tackle genomic instability in MND and pinpointing novel genes for intervention against associated pathology.