Protein misfolding underlies many incurable conditions such as Alzheimer’s disease and amyotrophic lateral sclerosis (ALS). The Greek startup ResQ Biotech is harnessing bacteria to test potential peptide treatments for these diseases.
There are many diseases that involve the faulty processing of proteins in the cell, leading the proteins to clump together and damage the tissue. Well known examples include Alzheimer’s disease, ALS, Parkinson’s disease and Huntington’s disease. Most of these conditions are difficult to treat; for example, many drugs have failed to tackle Alzheimer’s disease in clinical trials over the last decade.
“The biology of these diseases is complicated and not very well understood,” said Athina Oikonomidou, head of business development at the firm ResQ Biotech.
Another part of the problem is that traditional drug discovery techniques aren’t able to screen enough diverse molecules quickly enough. And even if a company detects a molecule that binds to a misfolded protein, it must check that the drug actually corrects the misfolding, which takes extra time and resources.
To solve these issues, ResQ was spun out from the National Hellenic Research Foundation in 2019. Oikonomidou has expertise in technology transfer and, prior to the foundation of the company, she coached the scientific co-founders on how to build a business developing treatments for protein misfolding diseases.
“It all came down to founding a company in order to raise money and take the programs into the clinic,” said Oikonomidou.
ResQ focuses on developing peptide drugs to address protein misfolding. The startup genetically engineers Escherichia coli (E. coli) bacteria to produce a peptide drug in addition to proteins linked to protein misfolding diseases, such as amyloid beta in the case of Alzheimer’s disease. The proteins are also engineered to fluoresce when they are correctly folded. If a peptide drug successfully prevents a protein from misfolding, the bacterium fluoresces, allowing the company to select that drug for further development.
“We let the live bacteria produce and screen the molecules,” said Oikonomidou. She added that the technique has the potential to screen up to tens of billions of drug candidates this way for any disease involving protein misfolding.
The company chose to work with peptide drugs whose structure forms a ring shape, called cyclic peptides. According to the company, this emerging class of drug enables the company to screen a highly diverse range of molecules and can bind more strongly to target proteins than do linear peptides.
ResQ’s lead candidate treatment for Alzheimer’s disease is undergoing proof-of-concept studies in animal models. The firm is also developing several candidates for the treatment of ALS, each one targeting a different misfolded protein.
The market potential for treating ALS, Alzheimer’s and other protein folding disorders is vast, and many companies are developing treatments for these conditions. There are also several players that are developing cyclic peptides, including Oryn Therapeutics for the treatment of rheumatoid arthritis, and Teitur Trophics for the treatment of Huntington’s and Parkinson’s disease.
At present, ResQ is seeking out funding for its seed round. According to Oikonomidou, it’s a challenge for ResQ to find this funding in the Greek ecosystem.
“It’s not such a well-known and developed ecosystem, and VC funds need you to be next door to work with you, especially at very early stages,” added Oikonomidou.
While Greece is home to many promising biotech innovations, the nation’s pharmaceutical industry is still largely based on producing generic drugs, and too little on drug development. Oikonomidou explained that there are plenty of examples of great science in the country, “just not enough people who can turn them into companies or into licensable products.”