# The therapeutic potential of Myoki, a novel peptide in muscle atrophy: mechanisms and applications

## TL;DR

Myoki, a synthetic peptide, shows promise in preventing muscle atrophy by improving muscle mass and strength in lab and clinical studies.

## Contribution

Myoki is a novel synthetic peptide shown to effectively mitigate muscle atrophy across in vitro, in vivo, and clinical models.

## Key findings

- Myoki promotes myotube differentiation and reduces muscle degradation in DEX-induced atrophy models.
- In SAMP8 mice, Myoki improved muscle fiber area and reduced fibrosis over 45 weeks.
- In a clinical trial, Myoki increased muscle mass, walking speed, and grip strength in patients with muscle atrophy.

## Abstract

With the global population rapidly aging, the prevalence of sarcopenia, referring to a progressive loss of skeletal muscle mass and strength, is increasing, highlighting the need for effective preventive and therapeutic strategies. In this study, we evaluated the efficacy of Myoki, a synthetic peptide, in muscle atrophy models in vitro, in vivo, and in a human clinical trial.

This study evaluated the therapeutic potential of Myoki, a synthetic peptide, in preventing muscle atrophy by assessing its effects in multiple models. In vitro, C2C12 myoblasts were used to evaluate Myoki’s impact on cytotoxicity, myotube differentiation, and muscle atrophy in DEX-induced atrophy models, with effects measured by western blot, qRT-PCR, and immunofluorescence. The binding affinity between Myoki and myostatin was further evaluated using surface plasmon resonance (SPR) and confirmed by ELISA-based assays. In vivo, the accelerated aging mouse model (SAMP8) was employed to investigate Myoki’s effect on muscle fiber area, collagen deposition, and muscle atrophy markers, with muscle histology, fibrosis, and fluorescence intensities of key proteins assessed via immunofluorescence after 45 weeks of treatment. In the clinical study, a randomized, double-blind, placebo-controlled trial was conducted with 80 patients diagnosed with muscle atrophy, who received Myoki (200 mg/day) or placebo for 12 weeks. Key efficacy endpoints included changes in muscle mass (DEXA), handgrip strength, walking speed (6-m walk test), and serum marker levels, with safety monitored throughout the trial.

Myoki demonstrated no cytotoxicity up to 500 μM in C2C12 cells and significantly promoted myotube differentiation. In DEX-induced muscle atrophy models, Myoki restored protein synthesis signaling and reduced muscle degradation pathways. In the SAMP8 mouse model, Myoki improved muscle fiber area, reduced collagen deposition, and mitigated muscle fibrosis. In the clinical trial, Myoki supplementation for 12 weeks significantly improved muscle mass, walking speed, and grip strength, along with favorable changes in serum markers related to muscle growth and damage.

Our results position Myoki as a promising potential candidate for mitigating muscle atrophy, including age-associated muscle loss. These findings support its therapeutic potential for conditions such as sarcopenia, making it a valuable candidate for further clinical exploration.

clinicaltrials.gov, CTRI/2024/01/061919.

Graphic titled “Efficacy of Myoki in Muscle Atrophy” divided into three sections. In vitro illustration showing C2C12 muscle cells, demonstrating the effects of Myoki in promoting differentiation, enhancing protein synthesis, decreasing protein degradation, and inhibiting myostatin. In Vivo features a mouse, muscle histology, increased cross-sectional area, and collagen deposition. Clinical Study includes patients, increased muscle mass, walking speed, grip strength, and improved serum markers. A note mentions Myoki as a synthetic peptide for muscle atrophy across in vitro, in vivo, and clinical models.