Greek researchers have identified a new drug candidate that restored learning and memory in preclinical animal studies involving Alzheimer’s symptoms, offering a potential new approach to treating the disease.
The molecule, known as RSQ-020, targets the Tau protein, which can misfold and form aggregates associated with Alzheimer’s and other serious neurodegenerative diseases.
The research team includes scientists from the Biomedical Sciences Research Center “Alexander Fleming,” the National Hellenic Research Foundation and Greek biotech spin-off ResQ Biotech. The team is led by Dr George Skretas, director of the Institute of Bioinnovation at the Biomedical Sciences Research Center “Alexander Fleming” and an associate researcher at the Institute of Chemical Biology of the National Hellenic Research Foundation.
A new approach to drug discovery
RSQ-020 emerged through a technology developed by the Greek research team that allows scientists to screen billions of potential molecules while simultaneously testing whether they can repair misfolded proteins.
Skretas explained to the Athens-Macedonian News Agency (AMNA) that conventional drug discovery for protein-misfolding diseases typically searches for a molecule that fits a specific target protein, much like a key fitting a lock.
The challenge, he said, is that proteins associated with neurodegenerative diseases do not maintain a fixed structure but constantly change shape.
Instead of searching for a molecule that fits a particular structure, the Greek team looks for molecules that actually perform the desired function.
The researchers produce the human protein of interest inside specially engineered bacteria. The bacteria emit light only when the protein stops misfolding properly. At the same time, the bacteria generate billions of different small molecules, each testing a different potential solution.
When a bacterial cell lights up, it signals that it contains a molecule that has worked.
“This means that instead of years of testing in test tubes, we can find molecules that work inside a living cell within days,” Skretas said.
From ALS research to Alzheimer’s
The technology initially focused on amyotrophic lateral sclerosis (ALS) and the SOD1 protein. However, the researchers designed the approach so that they could apply it to other diseases involving misfolded proteins.
These include Alzheimer’s disease, Parkinson’s disease and several other neurodegenerative conditions.
When the team applied the technology to the Tau protein, it identified RSQ-020.
Tau misfolding and aggregation play a major role in the cognitive decline associated with Alzheimer’s disease and other neurodegenerative disorders. Existing approved treatments primarily target another protein, beta-amyloid, and offer limited slowing of disease progression while carrying potential side effects.
Molecule restored learning and memory in animal models
ResQ Biotech, a biotechnology company spun out of the National Hellenic Research Foundation and led by Skretas, is now overseeing the preclinical development of RSQ-020.
One of the molecule’s most significant characteristics is that it appears to work after disease-related damage has already begun.
In experiments involving fruit flies that had already lost learning and memory abilities, treatment restored those abilities to levels seen in healthy animals. The improvement also continued for a substantial period after researchers stopped administering the molecule.
The molecule also broke down protein aggregates obtained directly from the brains of people who had died from neurodegenerative diseases.
Researchers observed this effect in Alzheimer’s disease as well as two rarer conditions: Pick’s disease, a form of frontotemporal dementia, and progressive supranuclear palsy.
Although Tau adopts different structures in these diseases, RSQ-020 proved effective against all the structures tested, according to Skretas.
He said this finding is significant because molecules designed to target one specific protein structure often fail when confronted with other structures.
Next step: Testing in mice
The researchers’ next step will examine whether RSQ-020 produces similar results in mice. That stage will require additional funding.
Skretas and ResQ Biotech received Proof of Concept funding from the European Research Council in 2024 to support the early stages of the research.
That same year, Lars Rasmussen, the investor and co-founder of Google Maps, also invested in the biotechnology company.
The researchers now need substantially more funding to advance the programme.
Skretas said the research began in a Greek laboratory with European funding and that a Greek company is developing the discovery. He warned that promising European discoveries often leave Europe at this stage because researchers lack the capital required to demonstrate their effectiveness.
If the molecule produces positive results in mice, the programme could then move relatively quickly towards the stages preceding human trials. Skretas estimates that results could potentially support the launch of clinical trials within the next three years.
Athens to host international protein-misfolding research meeting
The National Hellenic Research Foundation will host an international scientific meeting in Athens from October 12 to 15, 2026, focusing on protein misfolding and aggregation and their links to major human diseases.
The Athens School of Protein Misfolding Diseases will take place at the Airotel Stratos Vassilikos as part of the European Horizon project Twin4Promis, coordinated by the National Hellenic Research Foundation and Skretas.
The event will bring internationally recognised scientists from leading universities and research centres in Greece, Europe and the United States to Athens.
The programme will also include a free public event, “Protein Misfolding Diseases – Patient Challenges, Available Treatments and Therapeutic Development Landscape,” on October 12 at 3pm.
Scientists, clinicians, patients and caregivers will discuss protein-misfolding diseases, current treatment options and emerging research.
Skretas said the organisers want the public to understand the research taking place in Greek universities and research centres, the challenges faced by patients and caregivers, and the therapeutic approaches currently available and under development.
He said the organisers also want to convey a message of hope as research continues to advance potential treatments for these diseases.
