Drug repurposing is an effective strategy to address the global challenge of antimicrobial resistance.
In his recent doctoral thesis, defended at the University of Helsinki, Matej Zore investigated two drugs, fingolimod and etrasimod - initially developed to treat autoimmune diseases - for their potential to fight drug-resistant bacterial infections. Both drugs showed notable antibacterial effects, including against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE).
"By repurposing existing drugs, we aim to bypass some of the lengthy and expensive steps in traditional antibiotic discovery, offering a faster and more efficient way to address the urgent need for new treatments against drug-resistant bacteria. Since these drugs have already established safety and pharmacokinetic profiles, this approach could significantly reduce costs and shorten the development timeline compared to developing entirely new antibiotics," says Matej Zore from the Faculty of Pharmacy, University of Helsinki.
His research also involved designing and synthesizing derivatives of fingolimod and etrasimod, aiming to enhance their antibacterial potency. Notably, an etrasimod derivative was found to be especially effective against MRSA, with a low toxicity profile and a reduced likelihood of promoting resistance, a promising outcome in the search for new ways to tackle hard-to-treat infections.
"The drug repurposing approach we employed could be applied to other compounds as well, potentially accelerating the discovery of new antibacterial treatments. Drug repurposing has become an increasingly attractive strategy in antibiotic discovery, with researchers screening large libraries of approved and investigational drugs for antibacterial activity," Zore describes.
He emphasizes the urgent need for alternative therapies as resistance to current antibiotics rises, making many infections increasingly difficult to treat. His findings highlight the potential of drug repurposing to address this crisis by providing new antibacterial options, either as standalone treatments or in combination with existing antibiotics to enhance their effectiveness.
However, while drug repurposing presents an innovative and efficient strategy, it is important to recognize its limitations as well. "Although the potential is clear, it remains to be seen whether drug repurposing can become a viable solution in the fight against antimicrobial resistance," Zore points out.
Further studies are needed to understand the exact mechanisms by which these drugs act against bacterial cells and to evaluate their effectiveness in animal models.
Matej Zore defended his thesis " Drug repurposing to overcome antimicrobial resistance: the story of fingolimod and etrasimod " on 11.10.2024 at the Faculty of Pharmacy, University of Helsinki. Professor Fredrik Almqvist from Umeå University served as the opponent at the public examination and Professor Jari Yli-Kauhaluoma as the custos.
