Findings from the new study—published recently in the Journal of Medicinal Chemistry in an article entitled “Development of a Potent Wound Healing Agent Based on the Liver Fluke Granulin Structural Fold”—describes how the Australian scientists produced a version of the parasite molecule on a large enough scale to make it available for laboratory tests and eventually clinical trials. The molecule in question is called granulin, one of a family of protein growth factors involved in cell proliferation and secreted by the worms.
“It's produced by a parasitic liver fluke, Opisthorchis viverrini, which originally came to our attention because it causes a liver cancer that kills 26,000 people each year in Thailand," explained study co-author Michael Smout, Ph.D., a research fellow at James Cook University. "We realized the molecule, discovered in worm spit, could offer a solution for nonhealing wounds, which are a problem for diabetics, smokers, and the elderly."
The AITHM researchers found previously, as they were investigating a potential vaccine to protect people from the parasite, that granulin supercharged healing. The scientists looked for ways to produce the secreted molecule in sufficient quantities for large-scale testing. However, using traditional recombinant DNA techniques in bacteria wasn’t as straightforward as they had hoped.
"Unfortunately, granulin didn't perform well when we introduced it to Escherichia coli bacteria, so we couldn't use recombinant techniques to produce a testable supply," noted senior study investigator Norelle Daly, Ph.D., a professor at James Cook University, whose research involves exploring the potential of peptides as drug candidates for therapeutic applications. "We had to go back to the drawing board and find a way to synthesize part of the molecule—to build our own version of designer worm spit."
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