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Worm Spit Could Lead to Solution for Nonhealing Foot Ulcers

Researchers at James Cook University (JCU), Cairns, Australia, have reported that a molecule produced by a Thai liver parasite could be the solution to nonhealing wounds caused by diabetes-related foot ulcers, and scientists are now able to produce a version of the molecule on a large enough scale to make it available for laboratory tests and eventually clinical trials. The molecule is granulin, one of a family of protein growth factors involved with cell proliferation. The study describing this work was published April 20 in the Journal of Medicinal Chemistry.

“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,” said parasitologist Michael Smout, PhD, a research fellow with JCU’s Australian Institute of Tropical Health & Medicine (AITHM).

As part of their work on a potential vaccine to protect people from the parasite, Smout and colleagues established that the granulin it produces supercharges healing. “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,” he said.

With fellow researchers from the AITHM, Smout has been investigating ways to produce granulin in sufficient quantities for larger-scale testing. They worked to establish which parts of the molecule were critical to wound healing, and to find a way to reproduce the active parts of granulin molecules (peptides). Nuclear magnetic resonance (NMR) spectroscopy revealed the molecule’s complex shape: a string of amino acids bent into a twisted 3D shape that includes hairpin bends. After testing different segments and structures, the team concluded that those hairpin bends were the key.

“They’re held in the twisted 3D shape by disulfide bonds, and surprisingly we’ve found that by introducing an extra, nonnative, bond we can produce peptides that hold the right shape to promote healing,” said Norelle Daly, PhD, a professorial research fellow with AITHM whose research involves exploring the potential of peptides as drug candidates for therapeutic applications.

The lab-produced granulin peptides have shown promise in tests, driving cell proliferation in human cells grown in lab plates, and demonstrating potent wound healing in mice. Now that they can mass-produce these wound-healing peptides, the researchers said they are looking for potential partners as they progress toward further testing and eventually clinical trials.

Smout prepares cell cultures to test granulin’s cell proliferation properties. Photograph courtesy of JCU.

Editor’s note: This story was adapted from materials provided by JCU.