A new drug candidate molecule that, in preclinical studies, succeeded in restoring learning and memory abilities in animals displaying Alzheimer’s-like symptoms has been identified by Greek researcher Dr. George Skretas and a research team from the Biomedical Sciences Research Center “Alexander Fleming,” the National Hellenic Research Foundation, and the spin-off company ResQ Biotech. The molecule, RSQ-020, targets the tau protein, which, when misfolded and forming aggregates, is implicated in a number of serious neurodegenerative diseases.

RSQ-020 was discovered using a pioneering technology developed by the research team. The researchers have engineered bacteria to produce billions of candidate molecules while simultaneously screening them for functionality, enabling them to identify those capable of repairing proteins that have misfolded.

Explaining the innovative method, George Skretas, director of the Institute for Bioinnovation at the Biomedical Sciences Research Center “Alexander Fleming” and an affiliated researcher at the Institute of Chemical Biology of the National Hellenic Research Foundation, told the Athens-Macedonian News Agency (ANA-MPA):

“The conventional approach to drug discovery for diseases caused by protein misfolding is to look for a key, a drug candidate molecule, that fits a lock the target protein. However, these proteins, which are commonly associated with neurodegeneration, do not have a fixed lock; instead, they are constantly changing shape.

That is why, despite decades of research and billions of dollars invested, almost none of these diseases has a treatment capable of stopping its progression. We do not look for the key that fits the lock. We look directly for what does the job properly—that is, what opens the door. And how do we find it? We see the door opening: when that happens, a bright green light suddenly switches on inside our bacteria!”

In practical terms, the researchers produce the human protein of interest inside bacteria that have been engineered to light up only when the protein stops misfolding. At the same time, the bacteria themselves produce billions of different small molecules, with each one testing a different potential solution. Any cell that lights up indicates to the researchers that it contains a molecule that has worked.

“Thus, instead of spending years testing compounds in test tubes, we can identify molecules that work inside a living cell within just a few days in an environment that much more closely resembles the conditions of human disease than a test tube does,” Dr. Skretas notes.

The method was initially developed with a focus on ALS (amyotrophic lateral sclerosis) and a protein known as superoxide dismutase 1 (SOD1). However, its potential is not limited to ALS. Misfolded proteins are implicated in Alzheimer’s disease, Parkinson’s disease, and many other disorders, meaning that the same discovery process can be applied to any of these conditions.

Read the full story in Greek