A Halifax company is testing a new chemical compound that acts like a magnet to break down the defences of antibiotic-resistant superbugs by depriving them of the one thing they all need — iron.
Chelation Partners Inc. has been working for years on an iron-binding polymer it calls Dibi, and with the help of researchers at Dalhousie and Cape Breton universities, the compound is now in clinical trials using dogs with ear infections, said Bill Cheliak, one of the company’s founders.
Increasing numbers of antibiotic-resistant microbes are threatening human and animal health, and research into new drugs that treat infections is expensive and time consuming, he said.
“In the times before antibiotics, people played their chances and hoped their immune system was able to overcome (infection),” Cheliak said. “If it didn’t, they died.
“We’ve invested 75 years and countless hundreds of billions of dollars to develop antibiotics, and we have this big portfolio and we just can’t walk away from it. That’s just not a reasonable or rational thing to consider or contemplate, so how do you make it better?
“Because iron is needed regardless of what kind of pathogen you are — we call it an Achilles heel — so it’s common to all the different pathogens.
“It doesn’t matter if you’re a bacteria or a fungus; it doesn’t discriminate. All those guys need the iron and the only place they get it is from you, and if we’re successful in restricting it then we make these antibiotics work much better.”
Adding value to existing drugs provides a quicker and less expensive regulatory route to marketing pharmaceuticals, said Cheliak, and it results in a widely available medicine at a lower cost to consumers compared to brand-new drugs.
The company’s compound has been shown to bind with iron and weaken bacteria, suggesting it could be added to antibiotics to boost their effectiveness in the fight against infection, said Matthias Bierenstiel, an associate professor of inorganic chemistry at Cape Breton University.
“It’s amazing, the results there,” he said.
The polymer is a relatively large molecule that attracts and holds onto iron, Bierenstiel said. For comparison purposes, an Aspirin molecule might have a weight of 200 to 300 atomic units. Dibi weighs about 10,000 atomic units.
“Because it’s a large polymer and the iron is kind of hidden inside, we believe that it’s invisible to the bacteria because of the nature of this big, bulky polymer protecting it,” he said.
Without iron, infectious pathogens simply can’t grow or reproduce.
“This is a very simplified hypothesis, but it’s basically the basis of this,” said Bierenstiel.
The work at CBU has provided hands-on experience for undergraduate and honours students in Bierenstiel’s laboratory, helping develop manufacturing methods and studying how the polymer works at the molecular level.
“We developed the chemical pathway, so basically the recipe, in order to get there,” he said.
Now, Bierenstiel and his students are working on methods that would allow the manufacturing to scale up from lab conditions to a commercial environment.
Meanwhile, one of his postdoctoral students presented some research findings from the project at a national chemistry conference in Toronto earlier this summer, and another is scheduled to present at the American Society for Microbiology conference on antimicrobial resistance drugs in Boston next month.
And it has spurred a related project on microbial biofilms at the Verschuren Centre, CBU’s research institute.
Researchers in Dalhousie University’s faculty of medicine have also been involved with Chelation Partners and CBU, testing how the polymer works at the microbiological level in blood.
If animal tests are successful, human trials could be underway by the end of next year, Cheliak said.
“We’re thinking that we’ll be into human trials in 18 months,” he said. “That requires a couple of things to come together.
“There’s a full range of safety studies that the regulatory agencies will institute. The manufacturing part has to be made to certain standards that are applicable to the regulatory agencies. All that takes time.”