A research team from the
James Cook University has discovered a molecule called granulin produced by a
Thai liver parasite that could potentially offer a solution to the harrowing
problem of non-healing wounds, in diabetics.
‘A new molecule called granulin from the designer worm spit could be a solution to the non-healing wounds in diabetic patients.’
The research study was
published in the Journal of Medicinal Chemistry
Scientists are now
trying to produce a version of the granulin molecule on a large scale so that
it could be made available for laboratory tests and other clinical trials.
The Discovery of
Granulin To Heal Wounds
The granulin molecule
belongs to a family of protein growth factors that are involved in cell
Dr. Michael Smout, said,
"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."
While seeking a vaccine
to treat the liver parasite, the research team found granulin molecule to
Dr. Smout said, "We
realized the molecule, discovered in worm spit, could offer a solution for
non-healing wounds, which are a problem for diabetics, smokers and the
Investigating Ways To
To produce granulin
molecule in the required quantity for large-scale testing, the research team
tried to incorporate different techniques.
The scientists first
applied recombinant DNA technique that could effectively insert the granulin
into the bacteria that aimed in producing reliable copies of the molecule.
granulin molecule couldn't perform well when introduced into the E.coli
bacteria. Therefore, recombinant techniques couldn't be used to produce a
testable supply, said Professor Norelle Daly.
She also added that it
is essential to find a new way to synthesize only a part of the molecule that
could build an own version of the designer worm spit.
The scientists worked to
find out the critical part of the granulin molecule that is required for wound
healing. They also investigated ways to produce the active parts of the
The Key to Wound Healing
The complex shape of the
granulin molecule was revealed using Nuclear Magnetic Resonance (NMR)
The granulin molecule
was made up of a string of amino acids that are bent into a twisted 3D shape
which includes hairpin bends.
Dr. Smout said, that in
biology the shape and fold would vary the function of the molecule. And getting
the fold right could be like the difference between throwing a well-folded
paper plane and tossing a crumpled ball of paper.
After testing the
different segments, the research team concluded that hairpin bends were the key
to the wound healing activity.
Professor Daly said that
the hairpin bends were held in the twisted 3D shape by disulphide bonds,
Surprisingly, introducing an extra non-native bond could produce peptides and
hold the right shape to promote healing.
The granulin peptides
have shown great promise in tests; cell proliferation in human cells that are grown
in lab plates could also demonstrate potent wound healing in mice.
The research team can
now produce perfectly folded, wound healing properties. Further research may
progress towards further testing and clinical trials.
Professor Alex Loukas,
said, "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
Non-Healing Wounds in
In diabetic patients,
wounds heal very slowly. It is estimated that around 18 million Americans have
diabetes and around 15% of them may have a foot ulcer.
Around one in seven
diabetics in Australia will have a non-healing wound at some point of their
life and might have to undergo amputations.
About AU$3.7 billion per
year are involved in long hospital stays for treating chronic wounds.
Formulations like creams
with granulin molecule would be a great step to treat chronic wounds and will also
help to the reduce the burden on health care costs.
- Paramjit S. Bansal, Michael J. Smout, David Wilson, Claudia Cobos Caceres, Mohadeseh Dastpeyman, Javier Sotillo, Julia Seifert, Paul J. Brindley, Alex Loukas, Norelle L. Daly. Development of a Potent Wound Healing Agent Based on the Liver Fluke Granulin Structural Fold. Journal of Medicinal Chemistry, 2017; 60 (10): 4258 DOI: 10.1021/acs.jmedchem.7b00047
- How Diabetes Affects Wound Healing - (http://www.woundcarecenters.org/article/living-with-wounds/how-diabetes-affects-wound-healing)