The oral ghrelin receptor agonist HM01 reduced cisplatin- and motion-induced vomiting in shrews, especially when combined with standard anti-nausea medications.
1–30 mg/kg oral dosing effectiveHM01 reduced cisplatin- and motion-induced vomiting across this dose range when given orally, and enhanced standard anti-emetics at just 3 mg/kg
What the researchers found
HM01, an orally bioavailable ghrelin receptor (GHS-R1A) agonist that penetrates the brain, reduced emesis induced by cisplatin (30 mg/kg) and motion (1 Hz horizontal displacement) in Suncus murinus at doses of 1–30 mg/kg given orally.
Importantly, HM01 at just 3 mg/kg enhanced the anti-emetic effects of palonosetron alone and the palonosetron plus netupitant combination. However, HM01 was ineffective against emesis caused by nicotine or copper sulfate, indicating its anti-emetic action is selective to certain pathways. HM01 also improved food and water intake in animals treated with cisplatin or nicotine.
Why it matters
Chemotherapy-induced nausea and vomiting remains one of the most distressing side effects of cancer treatment, and current anti-emetic regimens don't fully control it in all patients. This study suggests that targeting the ghrelin pathway — a system primarily known for appetite regulation — could offer a new complementary approach. An oral, brain-penetrating ghrelin agonist that enhances existing anti-emetics could improve quality of life for chemotherapy patients while also addressing the appetite loss that commonly accompanies treatment.
How the study worked
Researchers used Suncus murinus (house musk shrews), an established animal model for studying vomiting since rodents cannot vomit. Animals were given HM01 orally at various doses (1–30 mg/kg) before being exposed to different emetic triggers: cisplatin injection, motion stimulation, nicotine injection, or copper sulfate gavage. Vomiting episodes were counted over observation periods, and food and water consumption were also measured. Combination experiments tested HM01 alongside standard anti-emetics palonosetron and netupitant.
What this study cannot tell us
This study was conducted in house musk shrews, not humans, so the results may not directly translate to clinical settings. The specific doses and drug interactions could differ significantly in people. The study also did not measure nausea directly (only vomiting episodes), and nausea is often the more persistent and harder-to-treat symptom. Additionally, long-term safety of repeated ghrelin agonist use and potential metabolic side effects like appetite changes were not assessed.
How to read the evidence
This is a preclinical animal study using an established emesis model (Suncus murinus). While the model is well-validated for vomiting research, findings in shrews require confirmation in human clinical trials before clinical relevance can be established.
When this study was published
Published in 2018, this study is relatively recent. Ghrelin agonist research for anti-emetic applications is still an active area, and these preclinical findings remain relevant as the field works toward clinical translation.
The bigger picture
This research fits into a growing interest in ghrelin-based therapies beyond appetite stimulation. While ghrelin and its analogs like anamorelin are already being explored for cancer cachexia, this study highlights the peptide hormone's potential in a completely different therapeutic area — anti-emetic therapy. If ghrelin agonists can enhance the effectiveness of current anti-nausea drug combinations, they could become part of standard chemotherapy supportive care protocols.
Questions still open
- Would HM01 or similar ghrelin agonists be effective against delayed-phase chemotherapy-induced nausea and vomiting in humans?
- Could the appetite-stimulating effects of ghrelin agonists provide a dual benefit for chemotherapy patients experiencing both nausea and cachexia?
- Why does HM01 reduce cisplatin- and motion-induced emesis but not nicotine- or copper sulfate-induced emesis, and what does this reveal about the ghrelin pathway's role in emesis?
Common questions
What is HM01 and how does it relate to ghrelin?
Why was this tested in shrews instead of mice or rats?
Read the original research
Anti-emetic Action of the Brain-Penetrating New Ghrelin Agonist, HM01, Alone and in Combination With the 5-HT3 Antagonist, Palonosetron and With the NK1 Antagonist, Netupitant, Against Cisplatin- and Motion-Induced Emesis in Suncus murinus (House Musk Shrew).
Frontiers in pharmacology, 9, 869
Citation
Rudd, John A; Chan, Sze W; Ngan, Man P; Tu, Longlong; Lu, Zengbing; Giuliano, Claudio; Lovati, Emanuela; Pietra, Claudio. (2018). Anti-emetic Action of the Brain-Penetrating New Ghrelin Agonist, HM01, Alone and in Combination With the 5-HT3 Antagonist, Palonosetron and With the NK1 Antagonist, Netupitant, Against Cisplatin- and Motion-Induced Emesis in Suncus murinus (House Musk Shrew).. Frontiers in pharmacology, 9, 869. https://doi.org/10.3389/fphar.2018.00869