The holy grail of pain relief?

In a world first, Australian-led researchers have discovered a fungus they believe can mimic opioids but with fewer side effects.

The global search for an opioid alternative has made a leap forward, according to an article in leading scientific journal PNAS, with the discovery in Australia of a fungus that can deliver effective pain relief but has far fewer addictive qualities, thus addressing an opioid epidemic of deaths by overdose.

The Australian Bureau of Statistics (ABS) reports that opioids accounted for just over three deaths per day in 2018. The majority were unintentional overdoses in middle-aged males involving the use of pharmaceutical opioids, it said.

A national strategy to combat addiction includes bans on purchases of over-the-counter codeine, but it seems that where there’s a will there’s a way, with one in 10 people believed to be using illegal opioids or misusing prescription drugs.

YourLifeChoices outlined research earlier in the year that showed older Australians who took antidepressants or opioids were more than twice as likely to suffer falls and hip fractures.

The fungus at the centre of this latest research was taken from an estuary in Tasmania’s pristine Huon Valley.

Analysis revealed a set of uniquely shaped tetrapeptides that mimic endomorphins – natural opioid neurotransmitters central to pain relief.

An international team led by the Universities of Sydney and Queensland developed this into a new opioid type considered a gold standard – but with fewer side effects – and created an effective analgesic for pain relief in the laboratory.

Drug companies have invested billions of dollars in the hunt for such a find, PNAS reports.

A patent application has been filed in Australia and further research, to confirm whether a new drug is in the making, is expected to be finalised within months.

Senior author Professor Macdonald Christie, from the University of Sydney’s faculty of medicine and health, said the findings were on the back of a decades-long search for “a holy grail of potential pain relief”.

“The structure we found has never been seen before,” said Prof. Christie, a pharmacologist with the School of Medical Sciences and Associate Dean Research.

From the fungus, the researchers discovered three versions of tetrapeptides, a chain of four amino acids (the molecular building blocks of life) joined by peptide bonds. But it was their curious molecular structure that caught the researchers’ attention.

In some molecules, geometric orientation is referred to as chirality or ‘handedness’. Molecules can be ‘left handed’ or ‘right handed’, mirror images of each other, but the way they are orientated makes a huge difference. In nature, almost all amino acids are ‘left handed’ in shape.

There are exceptions in nature, with molecules twisted in the ‘right hand’ orientation, but this is extremely rare in mammals. The ones that were found in the fungus were twisted in this unusual way.

Prof. Christie explained: “No one had ever pulled anything out of nature, anything more ancient than a vertebrate that seemed to act on opiate receptors – and we found it.”

The sample that prompted the research had been taken from the Tasmanian estuary as part of a program involving Professor Rob Capon, a natural products chemist from the University of Queensland’s Institute for Molecular Bioscience.

Prof. Capon had been part of a program that screened dirt and mud for microbes with biological activity and found the molecule from penicillium fungus isolated from mud next to a boat ramp.

Under the microscope, it looked like the molecules in our body that interact with the opioid receptor.

Prof. Christie said if follow-up testing was successful, as with any drug discovery, it could be a decade before this would result in a new medication available to the public.

Such a development could, however, have a major impact globally.

“If this proves successful and leads to a new medication, it will significantly reduce the risk of death by overdose from opioid medications such as codeine,” Prof. Christie concluded.

Have you had reason to take opioid-based medications? Was the possibility of a potential overdose spelt out to you?

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Written by Janelle Ward

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