A Greek-led research project has secured significant funding from the European Innovation Council (EIC) to develop a new technology that uses circular mini-proteins and artificial intelligence (AI) to discover potential treatments for diseases caused by mis-folded proteins, including Alzheimer’s disease and Parkinson’s disease.
The project, titled Mini Proteins against Mega Diseases (Mini-Me), combines the selection of circular mini-proteins that target misfolding-related diseases, the creation of billions of molecular variants and the simultaneous assessment of their properties. Researchers will then use AI to optimise the most promising candidates, creating a self-improving platform for therapeutic discovery.
More than 100 diseases are associated with abnormal protein folding, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), systemic amyloidosis and type 2 diabetes.
Despite their differences, these conditions share a common molecular mechanism. When proteins lose their normal three-dimensional structure, they can form aggregates that damage cells and tissues. Developing treatments that directly intervene in these processes remains a major scientific challenge.
Mini-Me aims to address this challenge by developing circular mini-proteins as a new class of potential therapeutic molecules and establishing a platform that continually improves its ability to discover and optimise them.
“Most current approaches search for molecules that simply bind to a target. In protein-folding diseases, however, this is not enough. We need molecules that can genuinely change the behaviour of a protein that misfolds and accumulates in toxic forms,” the project’s coordinator, Dr Georgios Skretas, told the Athens-Macedonian News Agency (AMNA).
Skretas directs the Institute of Bioinnovation at the Biomedical Sciences Research Centre (BSRC) Alexander Fleming.
“With Mini-Me, we want to demonstrate that we can design a new class of therapeutic molecules in a systematic, evolvable and biologically relevant way,” he added.
Mini-Me Builds on Promising RSQ-020 Drug Candidate
Mini-Me builds on an earlier discovery by Skretas’ research team: RSQ-020, a potential drug candidate that targets the Tau protein. When Tau misfolds and forms aggregates, it contributes to several serious neurodegenerative diseases.
In preclinical studies, RSQ-020 restored learning and memory abilities in animals displaying Alzheimer’s-like symptoms.
Skretas described Mini-Me as the natural continuation and technological advancement of the RSQ-020 discovery. The small circular peptide demonstrated that molecules of this type could intervene in the abnormal folding and aggregation of Tau.
While RSQ-020 provided an initial proof of concept, Mini-Me advances the approach by developing circular mini-proteins, a more complex class of molecules with greater structural complexity and the potential to target difficult protein targets more precisely.
The project aims to turn this technological advance into a broader discovery and optimisation platform for potential treatments for protein-folding diseases, including tauopathies and amyloidosis.
Two Disease Groups at the Centre of Research
Researchers will initially focus on two disease groups: tauopathies, which include Alzheimer’s disease and involve the abnormal aggregation of Tau in the brain, and immunoglobulin light-chain amyloidosis (AL amyloidosis), a serious condition that can damage vital organs.
By investigating these two applications, the team hopes to establish whether the same technological approach can work against different protein targets.
Preliminary findings have already shown promise.
For Tau, researchers have identified mini-proteins that inhibit its aggregation in experimental systems, break down fibrils derived from the brains of patients with Alzheimer’s disease and Pick’s disease, and reduce abnormal aggregation in human cell models.
For immunoglobulin light chains, the team has identified other mini-proteins that improve the stability of different protein variants and reduce the resulting cardiotoxicity in cell models.
These findings will underpin further optimisation and evaluation of the candidate molecules, as well as validation of the technology in subsequent stages of development.
The project consortium brings together eight partners from six European countries, including the University of Cambridge.
Greek biotechnology company ResQ Biotech will play a key role in translating the research into practical applications. As a principal commercialisation partner, the company aims to turn the findings into protectable know-how and potential therapeutic molecules, creating opportunities for further development, international partnerships and investment.
EIC Funding Selected from More Than 2,100 Proposals
The European Innovation Council selected Mini-Me for funding under its EIC Pathfinder Open programme, which received 2,103 proposals.
The EIC chose 43 pioneering projects from 30 countries to expand the boundaries of scientific discovery and lay the foundations for future transformative innovations.
Alongside Mini-Me, another Greek project, SENSEPACK from the Agricultural University of Athens, will receive funding.
“The fact that Mini-Me was selected in a call with a success rate of approximately 2% and is one of only two successful projects coordinated by Greece demonstrates that Greek biomedical research can stand at the forefront of European innovation,” Skretas said.
Funded projects can receive grants of up to €4 million and benefit from direct collaboration with EIC programme managers.
(Source: AMNA)
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