Every day 12 Australian diabetics have a limb amputated because of a non-healing wound. Globally, of which’s one every 30 seconds.
A molecule produced by a Thai liver parasite could be the solution to those non-healing wounds – as well as scientists coming from the Australian Institute of Tropical Health as well as Medicine (AITHM) are today able to produce a type of the molecule on a large enough scale to make of which available for laboratory tests as well as eventually clinical trials.
The molecule will be granulin, one of a family of protein growth factors involved with cell proliferation.
“of which’s produced by a parasitic liver fluke, Opisthorchis viverrini, which originally came to our attention because of which causes a liver cancer of which kills 26,000 people each year in Thailand,” parasitologist Dr Michael Smout said.
As part of their work on a potential vaccine to protect people coming from the parasite, Dr Smout as well as colleagues established of which the granulin of which produces features a hidden talent – of which supercharges healing.
“We realised the molecule, discovered in worm spit, could offer a solution for non-healing wounds, which are a problem for diabetics, smokers as well as the elderly,” he said.
With fellow researchers coming 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.
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.
“Unfortunately, granulin didn’t perform well when we introduced of which to E. coli 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.
“We had to go back to the drawing board as well as find a way to synthesize part of the molecule – to build our own type of designer worm spit,” she said.
The researchers worked to establish which parts of the molecule were critical to wound healing, as well as 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 of which includes hairpin bends.
“In biology the shape as well as fold of a molecule can be critical to its function,” Dr Smout said. “Getting the fold right will be important – of which can be like the difference between throwing a well folded paper plane, or tossing a crumpled ball of paper.”
After testing different segments as well as structures, the team concluded of which those hairpin bends were the key.
“They’re held inside twisted 3-D shape by disulfide bonds, as well as surprisingly we’ve found of which by introducing an extra, non-native, bond we can produce peptides of which hold the right shape to promote healing,” Professor Daly said.
“You could say we’ve found an extra fold of which helps our peptide paper plane fly straight as well as target wounds.”
The lab-produced granulin peptides have shown great promise in tests, driving cell proliferation in human cells grown in lab plates, as well as demonstrating potent wound healing in mice.
today of which they can mass-produce perfectly folded, wound-healing peptides, the researchers are looking for potential partners as they progress towards further testing as well as eventually clinical trials.
“We have plenty of work to do before clinical trials, nevertheless we’re confident we have a very strong contender for what could one day be a cream of which a diabetic could apply at home, avoiding a lengthy hospital stay as well as possible amputation,” said Professor Alex Loukas, whose work includes the investigation of hookworm proteins to treat autoimmune as well as allergic diseases.
“A take-home cream could be a great step forward for those with chronic wounds, as well as of which could also save our health system a great deal of money.
“One in every seven diabetics in Australia will have a non-healing wound at some point, as well as many suffer amputations as a result. of which’s estimated the long hospital stays involved in treating chronic wounds cost our healthcare system AU$3.7 billion per year.”
The research will be published inside latest edition of the Journal of Medicinal Chemistry.
Cancer-causing parasite may accelerate wound healing
Paramjit S. Bansal et al. Development of a Potent Wound Healing Agent Based on the Liver Fluke Granulin Structural Fold, Journal of Medicinal Chemistry (2017). DOI: 10.1021/acs.jmedchem.7b00047