{"id":178948,"date":"2017-05-25T16:08:50","date_gmt":"2017-05-25T16:08:50","guid":{"rendered":"http:\/\/healthmedicinet.com\/i\/a-molecule-produced-by-a-thai-liver-parasite-could-be-the-solution-to-those-non-healing-wounds\/"},"modified":"2017-05-25T16:08:50","modified_gmt":"2017-05-25T16:08:50","slug":"a-molecule-produced-by-a-thai-liver-parasite-could-be-the-solution-to-those-non-healing-wounds","status":"publish","type":"post","link":"http:\/\/healthmedicinet.com\/i\/a-molecule-produced-by-a-thai-liver-parasite-could-be-the-solution-to-those-non-healing-wounds\/","title":{"rendered":"A molecule produced by a Thai liver parasite could be the solution to those non-healing wounds"},"content":{"rendered":"
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Every day 12 Australian diabetics have a limb amputated because of a non-healing wound. Globally, it’s one every 30 seconds.\n <\/p>\n


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A molecule produced by a Thai liver parasite could be the solution to those non-healing wounds – and scientists from the Australian Institute of Tropical Health and Medicine (AITHM) 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.<\/p>\n

The molecule is granulin, one of a family of protein growth factors involved with cell proliferation<\/a>.<\/p>\n

“It’s produced by a parasitic liver fluke, Opisthorchis viverrini<\/i>, which originally came to our attention because it causes a liver cancer that kills 26,000 people each year in Thailand,” parasitologist Dr Michael Smout said.<\/p>\n

As part of their work on a potential vaccine to protect people from the parasite, Dr Smout and colleagues established that the granulin it produces has a hidden talent – it supercharges healing.<\/p>\n

“We realised the molecule, discovered in worm spit, could offer a solution for non-healing wounds, which are a problem for diabetics, smokers and the elderly,” he said.<\/p>\n

With fellow researchers from the AITHM at James Cook University in Cairns, Dr Smout has been investigating ways to produce granulin in sufficient quantities for larger-scale testing.<\/p>\n

The team first tried recombinant DNA techniques, effectively inserting granulin into bacteria, with the aim of producing plentiful supplies of a reliable copy of the molecule.<\/p>\n

“Unfortunately, granulin didn’t perform well when we introduced it to E. coli<\/i> bacteria, so we couldn’t use recombinant techniques to produce a testable supply,” said Professor Norelle Daly, whose research involves exploring the potential of peptides as drug candidates for therapeutic applications.<\/p>\n

“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,” she said.<\/p>\n

The researchers 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<\/a> (peptides).<\/p>\n

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.<\/p>\n

“In biology the shape and fold of a molecule can be critical to its function,” Dr Smout said. “Getting the fold right is important – it can be like the difference between throwing a well folded paper plane, or tossing a crumpled ball of paper.”<\/p>\n

After testing different segments and structures, the team concluded that those hairpin bends were the key.<\/p>\n

“They’re held in the twisted 3-D shape by disulfide bonds, and surprisingly we’ve found that by introducing an extra, non-native, bond we can produce peptides that hold the right shape to promote healing,” Professor Daly said.<\/p>\n

“You could say we’ve found an extra fold that helps our peptide paper plane fly straight and target wounds.”<\/p>\n

The lab-produced granulin peptides have shown great promise in tests, driving cell proliferation in human cells grown in lab plates, and demonstrating potent wound healing in mice.<\/p>\n

Now that they can mass-produce perfectly folded, wound-healing peptides, the researchers are looking for potential partners as they progress towards further testing and eventually clinical trials.<\/p>\n

“We have plenty of work to do before clinical trials, but we’re confident we have a very strong contender for what could one day be a cream that a diabetic could apply at home, avoiding a lengthy hospital stay and possible amputation,” said Professor Alex Loukas, whose work includes the investigation of hookworm proteins to treat autoimmune and allergic diseases.<\/p>\n

“A take-home cream would be a great step forward for those with chronic wounds<\/a>, and it would also save our health system a great deal of money.<\/p>\n

“One in every seven diabetics in Australia will have a non-healing wound<\/a> at some point, and many suffer amputations as a result. It’s estimated the long hospital stays involved in treating chronic wounds<\/a> cost our healthcare system AU$3.7 billion per year.”<\/p>\n

The research is published in the latest edition of the Journal of Medicinal Chemistry<\/i>.\n <\/p>\n

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\n Explore further:<\/b>
\n Cancer-causing parasite may accelerate wound healing<\/a>\n <\/p>\n

\n More information:<\/b>
\n Paramjit S. Bansal et al. Development of a Potent Wound Healing Agent Based on the Liver Fluke Granulin Structural Fold, Journal of Medicinal Chemistry<\/i> (2017). DOI: 10.1021\/acs.jmedchem.7b00047<\/a>
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