Oxytocin analogue treats chronic abdominal pain

Researchers have developed a new class of oral painkillers to suppress chronic abdominal pain, based on the peptide hormone known as oxytocin. Their innovation offers a safe, non-opioid-based solution for conditions such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), which affect millions of people worldwide.

The research team was led by Markus Muttenthaler, a medicinal chemist at the University of Vienna and The University of Queensland’s Institute for Molecular Bioscience. Their results have been published in the international edition of the journal Angewandte Chemie.

Current medications used to treat chronic abdominal pain often rely on opioids. However, opioids can cause severe side effects such as addiction, nausea and constipation, and also affect the central nervous system, often leading to fatigue and drowsiness. Therefore, there is an urgent need for alternatives that minimise these risks.

Oxytocin 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. Oxytocin can also affect pain perception as, when it binds to receptors in the gut, it triggers a signal that reduces pain signals. The advantage of this approach is that the effect is gut-specific, thus having a lower risk of side effects due to its non-systemic, gut-restricted action.

At the moment, most peptide drugs (such as insulin and GLP1 analogues) must be injected as they are rapidly digested in the gut. Now, Muttenthaler’s team has created oxytocin compounds that are fully gut-stable yet can still potently and selectively activate the oxytocin receptor.

“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,” Muttenthaler explained.

“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 team’s 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. According to Muttenthaler, “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.”

With support from the European Research Council, the scientists are now working to translate their research findings into practice. The goal is to bring these new peptides to market as an effective and safe treatment for chronic abdominal pain. Moreover, the general approach of oral, stable and gut-specific peptide therapeutics could revolutionise the treatment of gastrointestinal diseases, as the therapeutic potential of peptides in this area has not yet been fully explored.

The team has already secured a patent for the developed drug leads and is now actively seeking investors and industrial partners to accelerate preclinical studies, with the goal of taking the drugs 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,” Muttenthaler said.

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