Ghrelin-Based Drug HM01 Reduces Chemotherapy and Motion-Induced Vomiting in Animal Model
The oral ghrelin receptor agonist HM01 reduced cisplatin- and motion-induced vomiting in shrews, especially when combined with standard anti-nausea medications.
Quick Facts
What This Study 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.
Key Numbers
How They Did This
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.
Why This Research 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.
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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- 1–30 mg/kg oral dosing effective HM01 reduced cisplatin- and motion-induced vomiting across this dose range when given orally, and enhanced standard anti-emetics at just 3 mg/kg
- Evidence Grade:
- 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.
- Study Age:
- 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.
- Original Title:
- 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).
- Published In:
- Frontiers in pharmacology, 9, 869 (2018)
- Authors:
- Rudd, John A(2), Chan, Sze W, Ngan, Man P(2), Tu, Longlong, Lu, Zengbing, Giuliano, Claudio, Lovati, Emanuela, Pietra, Claudio
- Database ID:
- RPEP-03873
Evidence Hierarchy
Frequently Asked Questions
What is HM01 and how does it relate to ghrelin?
HM01 is a synthetic small molecule that mimics ghrelin, the 'hunger hormone,' by activating the same receptor (GHS-R1A) in the brain. Unlike ghrelin itself, HM01 can be taken orally and readily crosses into the brain, making it a more practical drug candidate.
Why was this tested in shrews instead of mice or rats?
House musk shrews (Suncus murinus) are used because mice and rats physically cannot vomit. Shrews are one of the smallest mammals that can, making them a standard model for studying nausea and vomiting treatments.
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Cite This Study
https://rethinkpeptides.com/research/RPEP-03873APA
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
MLA
Rudd, John A, et al. "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, 2018. https://doi.org/10.3389/fphar.2018.00869
RethinkPeptides
RethinkPeptides Research Database. "Anti-emetic Action of the Brain-Penetrating New Ghrelin Agon..." RPEP-03873. Retrieved from https://rethinkpeptides.com/research/rudd-2018-antiemetic-action-of-the
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Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.