Delivered through the national CUREator+ Dementia and Cognitive Decline BioMedTech Incubator, the funding will accelerate SynaptraBIO’s efforts to develop new, patient-friendly drugs that target the molecular drivers of neurodegeneration.
Founded by researchers Professor Lars Ittner, Dr Janet van Eersel and Dr Ole Tietz of Macquarie University’s Dementia Research Centre, SynaptraBIO builds on two decades of pioneering investigation into how abnormal protein build-ups outside brain cells and tangled protein fibres inside them work together to damage the connections that allow nerve cells to communicate.
By focusing on the chemical cascade that sparks this damage, the team is working to translate their discoveries into therapies that can slow or stop the progression of disease – in a form that could be as simple as an oral tablet.
Alzheimer’s disease, the most prevalent form of dementia, is known to be associated with characteristic chemical and physical changes in and around nerve cells (neurons) in the brain.
Plaques containing the peptide amyloid-β (Aβ) form outside neurons and are especially harmful at the synapses where neurons communicate with each other, disrupting signalling and weakening connections.
At the same time, tangles made up of the protein tau, normally associated with microtubules, form within cells.
Research by the Macquarie University group and others has shown that interactions between Aβ and tau initiate an ‘excitototoxic’ chemical cascade around the synapses that leads to dysfunction, toxicity and eventual death of neurons.
SynaptraBIO co-founder Professor Ittner and his colleagues identified disruption of this signalling cascade as a promising target for disease-modifying treatments.
“We’ve previously shown that modifying the structure of tau at a specific site inhibits Aβ excitoxicity in neurons,” says Professor Ittner.
“That suggested a potential therapeutic approach and we’ve been able to show that structurally modifying tau through gene therapy alleviates existing Aβ-induced memory impairment in mouse models of Alzheimer’s disease.”
Dr Tietz and his team have taken this proof of concept and worked to develop more practical and patient-friendly treatment options based on small molecules.
“Now, using our AI-powered drug discovery platform, we’re ‘reverse engineering’ with the aim of identifying small molecules that can be taken orally to achieve the same result,” says Dr Tietz.
The CUREator+ funding, announced today, will support the identification of several candidate molecules and assessment of their bioavailability, activity and toxicity in the laboratory.
Suitable molecules will then be tested by SynaptraBIO for their impact on memory, cognition and social behaviour in a pre-clinical animal model of Alzheimer’s disease, before one or more are selected as the basis for an investigational new drug (IND) application, a necessary prelude to administering a drug in human clinical trials.
These drugs will offer several advantages in comparison to existing treatments for dementia, says SynaptraBIO co-founder Dr van Eersel.
“The only disease-modifying therapies for Alzheimer’s disease that are currently available clinically or in late-stage clinical development are monoclonal antibodies,” she says.
“As well as being very expensive, those treatments have to be given by intravenous infusion, and patients need to be monitored carefully – including having regular brain scans – because of the risk of adverse effects.”
SynaptraBIO’s mission is to transform devastating neurodegenerative brain diseases into curable conditions through novel research-based therapies.
“We set out to develop a small molecule, orally bioavailable treatment for dementia and we’re excited to be going further on this great journey with the help of this vital funding,” says Dr Tietz.
“Ultimately, we hope our work can make a real difference to people with Alzheimer’s disease and their families.”
