ART x SCIENCE 2024 #39
Whisper of the Heart

Listen closely, the heart is beating rhythmically. These are calming whispers that reassure us we are living. 70 million people worldwide are affected by epilepsy. Despite over 20 anti-seizure medications available in Australia and worldwide, one-third of the patient population have drug-resistant epilepsy (DRE) and continue to have uncontrollable seizures.

Body area Heart

Impact

Our multidisciplinary collaboration across Murdoch Children’s Research Institute, Monash University and Swinburne University brings together experts in stem cell biology, neurology, cardiology, pharmacology and medicinal chemistry. We strive to develop an entirely new class of anti-seizure medications tackling DRE.

reNEW research

Currently, the adenosine A1 receptor (A1R) is a popular therapeutic target for developing novel anti-epileptic medication. However, A1R is not only expressed in the brain but also in the heart. We used wild-type and receptor knockout induced pluripotent stem cell-derived (iPSC-derived) neurons to assess on-target neuronal activity. We also differentiated the iPSCs into cardiomyocyte monolayers and cardiac organoids to screen drug candidates without off-target cardiotoxicity.

Image description

With the structures of the M-band (OBSCN in red), Z-disc (α-Actinin in green) and the connections with other neighboring cells (nuclei in blue), our iPSC-derived cardiomyocytes form a beating cardiac monolayer.

Credits

Yinghan (Winnie) She, David Elliott, Heart Regeneration and Disease Group, reNEW in collaboration with Ben Rollo’s lab and Lauren May’s lab from Monash University, Melbourne, Australia. Knock out iPSC lines generated by MCRI Stem Cell Core.