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This study evaluates the effects of HM17321, a CRFR2-selective UCN2 analog, on sarcopenia in SAMP8 mice.

June 7, 2026

1783-P: HM17321, a CRFR2 Selective UCN2 Analog, Prevents Muscle Loss and Functional Decline in Sarcopenic Mice

Key Points

This study evaluates the effects of HM17321, a CRFR2-selective UCN2 analog, on sarcopenia in SAMP8 mice.
Male SAMP8 mice were administered HM17321 subcutaneously for 4 months
Compared with age-matched SAMR1 controls
Skeletal muscle atrophy assessed by histology and muscle function assessed longitudinally
SAMP8 mice showed increased muscle degeneration and functional decline compared to SAMR1
HM17321 increased lean mass by up to +7.9% while reducing fat mass by up to -23.0%
In a dexamethasone model, HM17321 outperformed bimagrumab in preventing muscle functional impairment.

Abstract

Introduction and Objective: Sarcopenia is characterized by progressive deterioration of skeletal muscle mass, structural integrity and function. Senescence-accelerated mouse-prone 8 (SAMP8) mice represent accelerated aging model that recapitulates key features of sarcopenia. HM17321 is a CRFR2-selective UCN2 analog with established metabolic benefits and emerging relevance to skeletal muscle health. This study evaluated the effects of HM17321 on aging-associated sarcopenia in SAMP8 mice and its efficacy across complementary models of muscle atrophy. Methods: Male SAMP8 mice were subcutaneously administrated with HM17321 for 4 months, with senescence-resistant SAMR1 mice as age-matched controls. Body composition, neuromuscular function and aging-associated pheontypes were longitudinally assessed. Skeletal muscle atrophy was evaluated by histological analysis. The efficacy of HM17321 against muscle wasting was further assessed in a dexamethasone-induced muscle atrophy model. Results: Relative to SAMR1 mice, SAMP8 mice exhibited accelerated skeletal muscle degeneration and function decline. HM17321 broadly ameliorated these age-associated deficits, increasing lean mass (up to +7.9% vs. SAMP8 vehicle) while reducing fat mass (up to -23.0%), with concomitant enhancements in muscle performance, including grip strength and holding impulse, as well as attenuation of kyphosis and hindlimb clasping. These improvements were supported by preserved muscle architecture, with maintained myofiber cross-sectional area and laminin expression, and reduced MuRF1 in the gastrocnemius muscle. Consistently, in a dexamethasone-induced muscle atrophy model, HM17321 mitigated functional impairment more effectively than bimagrumab, supporting its protective effect on skeletal muscle under catabolic conditions. Conclusion: HM17321 attenuated sarcopenia across multiple etiologies by preserving muscle mass, function, and structural integrity. These findings support the potential of HM17321 as a therapeutic approach for sarcopenia. Disclosure D. Lee: None. Y. Kim: None. H. Kwon: Employee; Current; Hanmi Pharm. Co., Ltd. E. Park: Employee; Current; Hanmi Pharm. Co., Ltd. J. Kim: Employee; Current; Hanmi Pharm. Co., Ltd. J. Kim: None. S. Bae: None. S. Lee: Employee; Current; Hanmi Pharm. Co., Ltd. I. Choi: None.

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