Daryl Ariawan
Pre-clinical development of novel cell-penetrating peptides to block tau-associated neurotoxicity for the treatment of dementia

Award
Bondi2Berry Project Grant
Status
Completed
Start Date
1 April 2023
About the project
Key features of Alzheimer’s disease are the build-up of harmful proteins called amyloid-beta and tau, which lead to brain cell death. While many drug trials targeting amyloid-beta have failed, tau has become a new focus for treatment research.
Scientists have discovered that tau interacts with an enzyme called Fyn, which activates a brain cell receptor called NMDAR. This causes the receptor to link with another protein, called PSD-95, making the receptor more stable and increasing the signals the brain cell receives. Too much signalling can overwhelm brain cells, leading to seizures and cell death. A small molecule called NR2B9c can block this harmful chain reaction, protecting brain cells.
In this project, Dr Daryl Ariawan improved the stability of NR2B9c by attaching it to a new type of peptide. This new version was successfully delivered to the brain in animal tests. It also protected mouse brain cells from damage caused by both amyloid-beta and overactive receptors – and it was shown to be safe. In mice with seizures, the treatment reduced seizure severity and helped the mice live longer.
Dr Ariawan plans to continue this work on a larger scale, testing how well the treatment works long-term in Alzheimer’s disease models. This research could lead to important breakthroughs in understanding Alzheimer’s disease and developing new treatments.

Where are they now?
At the time of this award, Dr Daryl Ariawan worked with Professor Lars Ittner at Macquarie University on developing novel peptide therapeutics to treat Alzheimer’s disease.