Queensland researchers have developed a new class of oral painkillers based on the hormone that drives childbirth contractions.
A new class of oral painkillers to suppress chronic abdominal pain, based on the peptide hormone oxytocin that drives childbirth contractions, has been developed by researchers at the University of Queensland.
Associate Professor Markus Muttenthaler from UQ’s Institute for Molecular Bioscience led a team that has changed the chemical structure of oxytocin to make it gut-stable after earlier work revealed the hormone could treat abdominal pain.
They published their research in the international edition of Angewandte Chemie, a journal of the German Chemical Society.
“Abdominal pain presents an onerous reality for millions of people affected by gastrointestinal disorders such as irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD),” they wrote.
“The oxytocin receptor (OTR) has emerged as a new analgesic drug target with OTR expression upregulated on colon-innervating nociceptors in chronic visceral hypersensitivity states, accessible via luminal delivery.
“However, the low gastrointestinal stability of OTR’s endogenous peptide ligand oxytocin (OT) is a bottleneck for therapeutic development.”
Dr Muttenthaler said there was an urgent need for new treatments for the chronic pain caused by gastrointestinal disorders such as IBS and IBD.
“This pain affects up to 15% of adults in their lifetime and all we have are anti-inflammatories and opioids, which can cause side effects and addiction,” he said.
“Our research focuses on peptides that are highly potent and selective molecules that have few side effects. However, nearly all peptide drugs must be injected as they are rapidly digested in the gut.
“We have now developed a way of making peptides gut-stable so they can be given orally. This is a new and highly promising approach to treating gut disorders.”
Oxytocin is a peptide hormone produced in the brain which is known as the ‘bonding hormone’ or the ‘love molecule’ due to its effects on relationship building, empathy and trust.
It is also the key hormone that induces uterine contractions during labour and facilitates milk release during breastfeeding.
“We identified the parts of oxytocin that are rapidly broken down by gut enzymes and used medicinal chemistry to render them gut-stable while ensuring that the new molecule was still able to activate the oxytocin receptor,” said Dr Muttenthaler.
“We now have a new class of molecules that are potently active but do not degrade in the stomach or intestine, meaning they can be taken orally.”
The research indicates that the new molecules work in the colon and do not need to cross the gut barrier into the bloodstream to suppress abdominal pain.
“This is a very safe therapeutic approach as it reduces the risk of side effects in the rest of the body, a problem with many other systemic drugs,” said Dr Muttenthaler.
“This is an exciting new mode of action to prevent pain. We are currently looking for investors to accelerate pre-clinical studies, with the goal of taking it into the clinic.
“Now that we have perfected making peptides stable, we are looking at other gut drugs to improve treatment options for gastrointestinal disorders, an unmet medical need.”
