A research team at the University of Vienna, led by medicinal chemist Markus Muttenthaler, has developed a new class of oral peptide therapeutic leads for treating chronic abdominal pain. This groundbreaking innovation offers a safe, non-opioid-based solution for conditions such as irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD), which affect millions of people worldwide. The research results were recently published in the international edition of the renowned journal Angewandte Chemie.
An innovative approach to pain management
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. Additionally, they affect the central nervous system, often leading to fatigue and drowsiness, which impairs the quality of life of those affected. The addiction risk is particularly problematic and has contributed to the ongoing global opioid crisis. Therefore, there is an urgent need for alternatives that minimise these risks.
This new therapeutic approach targets oxytocin receptors in the gut. Oxytocin is commonly known as the ‘love hormone’ because of its role in social bonding. Less well-known is that oxytocin can also affect pain perception. When the peptide hormone oxytocin binds to these receptors, it triggers a signal that reduces pain signals in the gut. 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.
Oxytocin itself cannot be taken orally because it is rapidly broken down in the gastrointestinal tract. However, Prof. Muttenthaler’s team has successfully created oxytocin compounds that are fully gut-stable yet can still potently and selectively activate the oxytocin receptor. This means these newly developed oxytocin-like peptides can be taken orally, allowing for convenient treatment for patients. This approach is especially innovative since most peptide drugs (such as insulin, GLP1 analogues) need to be injected as they are also quickly degraded in the gut.
Our research highlights the therapeutic potential of gut-specific peptides and offers a new, safe alternative to existing pain medications, particularly for those suffering from chronic gut disorders and abdominal pain.”
Markus Muttenthaler, medicinal chemist
Next steps and future outlook
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 advance the drug leads towards the clinic.
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Journal reference:
Kremsmayr, T., et al. (2024). Oxytocin Analogues for the Oral Treatment of Abdominal Pain. Angewandte Chemie International Edition. doi.org/10.1002/anie.202415333.
