Funding amount $2,288,000

Alzheimer’s disease is the most common form of dementia without effective treatments. We have developed a novel drug candidate for dementia that blocks a central disease process to effectively prevent loss of brain cells. This CUREator+ project will undertake critical research and development to transition the drug candidate to commercialisation and clinical translation, eventually benefiting those living with dementia.

Alzheimer’s disease is a growing health challenge, with more than 400,000 Australians currently living with dementia and numbers expected to rise. Despite urgent need, effective treatments remain limited, and many approaches have not delivered meaningful benefits.

Our research is focused on a new way to tackle Alzheimer’s by targeting harmful processes at the connections between brain cells (synapses), where damage first occurs. We have identified a specific group of proteins that drive this toxicity and used advanced technologies, including artificial intelligence, to develop a promising drug candidate that can block this damaging pathway.

We are now working to advance this promising candidate towards becoming a treatment. This includes testing how well it works in Alzheimer’s models, assess its safety, and understanding how it behaves in the body. We will also generate essential data needed to progress into human clinical trials.

By accelerating the development of this novel approach, we aim to deliver a new, effective treatment option and ultimately improve the lives of people living with dementia and their families.

Back in 2006, we uncovered a new pathway that existed – identifying a molecular link between amyloid plaques and tau tangles as a potential therapeutic target. We developed a deep understanding of a critical molecular cascade which makes neurons (brain cells) vulnerable and have developed blockers of this cascade to help protect neurons, showing you could halt disease progression in diverse dementia models and recover lost functions for impaired neurons.

In SynaptraBIO, we are developing small molecules which could translate into drugs. While we are still in the early stages of drug development, our molecules show efficacy in dementia models.

Our goal is to create a therapeutic that’s patient-friendly, for example a daily pill to take. Drug development has changed majorly; there’s now a real focus on patient-centric outcomes. Working with consumer groups and patients at the earliest drug development stages is important because if we engage at this stage we can help meet their primary needs later. It’s mutually beneficial in modern day drug development.

One of the challenges we faced was that we had to build a new drug discovery platform, because the targets are not amenable to traditional drug pipelines. We have been able to get key structural information to let us identify a series of drug candidates, which we are currently taking through pre-clinical pipelines and ultimately to clinical trials (which is the long-term goal).

We are currently identifying lead compounds, optimising them and will be selecting the best ones to take forward.

Another key element of our project is that the molecular cascade we are targeting has not yet been used for dementia drug development. Our lead compounds have been amazingly effective in pre-clinical disease models, restoring some function, slowing the disease progression, and halting it in some cases. Our approach is best described as disease modifying.

Ours is a good example of why funding basic research is so important. Understanding the basic disease processes is vital, and there is no way to get to where we are without funding for basic research. For example, the fundamental work for this project was supported by initial fellowship funding by Dementia Australia in 2011.

There are a multitude of reasons why we work in this area, both professional and personal. At our core, researchers are kids at heart. We are curious and we want to see things that nobody has seen before. Pushing the boundaries is so satisfying and keeps us going to ultimately deliver therapies that change lives.