The Dementia Research Centre at Macquarie University will receive $200,000 to support research exploring the relationship between two key proteins within nerve cells (neurones) that are implicated in neurodevelopmental disorders and neurodegenerative diseases, including dementia.
To be allocated across 18 months, the grant from Syngap Research Fund Australia will allow researchers to investigate in detail the interactions between the proteins tau and synaptic ras GTPase-activating protein 1 (SynGAP1), each of which is known to play an important role in nerve cell function.
Mutations of the SYNGAP1 gene that lead to reductions in levels of SynGAP1 in developing neurones are known to cause intellectual disability with comorbid autism spectrum disorder and epilepsy.
Diminished levels and function of SynGAP1 protein at the synapse – where neurones transmit signals to one another – disrupt critical periods of growth and maturation, leading to developmental brain disorders with impairment of learning, memory and social function.
More than 1600 people worldwide, including 47 in Australia, are known to have SynGAP1-related disorders, and the number of diagnosed 'Syngapians' is growing rapidly due to more widespread use of genetic testing, greater clinician and public awareness, and advocacy by families and patient organisations.
Dysfunction of tau, a protein associated with stabilising microtubules inside neurones, is a known hallmark of several neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia.
By investigating how tau interacts with SynGAP1 at synapses, the project aims to reveal new mechanisms relevant not only to SynGAP1-related disorders but also to conditions marked by cognitive decline.
Professor Lars Ittner, who will lead the research together with Dr Janet van Eersel, says understanding and modulating these interactions may open the door to innovative therapies for both SynGAP1-related disorders and dementia.
"Our goal is to develop novel gene therapy approaches that can enhance the function of SynGAP1 in complexes within the cell," says Professor Ittner, Director of the Dementia Research Centre.
"At the same time, we're also aiming to find ways to reduce the inhibitory effects of tau on SynGAP1.
"This dual approach could unlock new pathways for treating SynGAP1 encephalopathies."
The project will involve the creation of innovative gene therapy vectors, building a foundation for future targeted treatments.
"We are committed to accelerating the development of safe and effective treatments for SynGAP1," says Danielle Williams, President of Syngap Research Fund Australia and a mother of two Syngapians.
Syngap parents Jennifer Murphy and Danielle Williams of Syngap Research Fund Australia (standing, left of banner) with Dr Janet van Eersel (standing, right of banner) and other researchers from Macquarie University's Dementia Research Centre.
Syngap Research Fund Australia is run by parents of Australian Syngapians and its activities include raising funds to support SynGAP1-related scientific research.
"This grant, which will be administered by the Epilepsy Foundation, represents a significant investment in Australian-based scientific innovation aimed at understanding and treating this rare neurological condition," says Mrs Williams.
"Supporting innovative research like this project at Macquarie University is central to our mission.
"The fact that the project also holds promise for broader neurodegenerative conditions, including dementia, is a bonus for the Australian community."
