RSQ-020, a new compound created by a Greek research team, restored learning and memory capacity in animal models that mimic Alzheimer’s disease, according to pre-clinical tests.
The effort combined scientists from the Alexander Fleming Biomedical Sciences Research Centre, the National Hellenic Research Foundation and the spin-off firm ResQ Biotech.
The agent works by acting on the tau protein, whose abnormal folding and aggregation are linked to the onset and progression of serious neurodegenerative disorders. Tau misfolding is a well-known hallmark of several brain-degenerative conditions, making it a strategic target for therapeutic intervention.
Discovery relied on a platform that employs engineered bacteria capable of producing billions of candidate molecules while signalling any that correct a faulty protein. The system flags successful hits with a green fluorescence. When a molecule restores the protein’s normal shape, the bacterial cell emits a visible green signal that can be detected automatically.
Read Also: Owkin shares AI and patient data tools with Servier
“Classical drug development is based on finding a molecule that “fits” a specific protein target, like a key in a lock,” said Giorgos Skretas, director of the Institute of Bioinnovation at the Fleming centre. “However, the proteins involved in misfolding diseases do not have a stable shape but change constantly, which makes it particularly difficult to develop effective treatments. Instead of simply looking for a molecule that will bind to a specific site on the protein, we look directly for one that delivers the desired effect,” he added.
In practice, researchers inserted a human protein into a bacterium and programmed it to glow only when the protein returned to a more normal conformation. Simultaneously, each cell generated a vast library of small molecules, allowing rapid identification of active agents inside living cells. The glowing read-out provides a real-time indicator that the protein has assumed a healthier structure.
The technology was initially developed with a focus on amyotrophic lateral sclerosis (ALS) and the SOD1 protein, and its potential applications extend to many other neurodegenerative conditions such as Alzheimer’s, Parkinson’s and other disorders where protein misfolding is a hallmark.
