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September 14, 2026Journal of Cachexia Sarcopenia and MuscleOpen Access

Myostatin inhibition restores muscle mass in ADCNM mice but fails to improve muscle force.

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Why the study?

Autosomal dominant centronuclear myopathy caused by DNM2 mutations leads to progressive muscle weakness and atrophy, and the therapeutic potential of myostatin inhibition in this condition was evaluated.

Does genetic or pharmacological inhibition of myostatin restore muscle mass and function in a mouse model of ADCNM?

Population

Mouse model of ADCNM caused by DNM2 mutations (KI mice)

Comparison

Genetic deletion of myostatin (KIKO mice) and pharmacological inhibition with sActRIIB-Fc vs untreated KI mice and wild-type mice

Design

Preclinical experimental study

Follow-up

4 weeks of treatment with observation up to 5 weeks post-treatment

Key result

Genetic and pharmacological inhibition of myostatin restored muscle mass in a mouse model of ADCNM, though pharmacological treatment did not improve muscle force or key pathological features.

Authors

DADurieux Anne‐CécileUniversité Claude Bernard Lyon 1ADArnould DavidUniversité Claude Bernard Lyon 1VMVelarde MathiasUniversité Claude Bernard Lyon 1

Discussion

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Overview

No immediate clinical role in ADCNM; leaves open whether combined approaches can restore function beyond mass.

Key Points

  • To determine whether genetic or pharmacological inhibition of myostatin can reverse muscle hypotrophy and functional deficits in a dynamin 2-related centronuclear myopathy mouse model.
  • Evaluated dynamin 2 knock-in (KI) mice, wild-type controls, and double-mutant mice with genetic deletion of myostatin (KIKO).
  • Administered pharmacological myostatin inhibitor sActRIIB-Fc twice weekly to KI mice starting at 4 weeks of age for a 4-week duration.
  • Assessed tibialis anterior muscle mass, histology, molecular pathways, and contractile function using magnetic resonance imaging and immunohistochemical analyses.
  • KI mice exhibited impaired postnatal growth with persistent muscle hypotrophy (-15%, p < 0.05), reduced satellite cells (-53%, p < 0.001 at 1 month; -68%, p < 0.01 at 2 months), and elevated Trim63 (+50%, p < 0.001; +87%, p < 0.001) and Fbxo32 (+39%, p < 0.05; +95%, p < 0.001) mRNA at 1 and 2 months.
  • Genetic deletion of myostatin fully restored muscle mass and normalized contractile function back to wild-type levels.
  • Pharmacological sActRIIB-Fc transiently restored muscle mass to wild-type values via Akt-mTOR activation, but mass returned to baseline 5 weeks post-treatment without improving muscle force, mitochondrial structure, or excitation-contraction coupling.

Structured PICO

Does genetic or pharmacological inhibition of myostatin restore muscle mass and function in a mouse model of ADCNM?

P
Population
Mouse model of ADCNM treated with genetic or pharmacological myostatin inhibition starting at 4 weeks of age for 4 weeks.
I
Intervention
Genetic deletion of myostatin (KIKO mice) and pharmacological inhibition with sActRIIB-Fc (twice weekly starting at 4 weeks of age for 4 weeks)
C
Comparator
Wild-type mice and untreated KI mice
O
Outcome
Muscle mass and muscle functionsurrogate

Myostatin inhibition can restore muscle mass in a mouse model of ADCNM, but pharmacological inhibition alone does not improve muscle force or underlying pathological features.

Cite This Study

Anne‐Cécile et al. (2026) studied Autosomal dominant centronuclear myopathy (ADCNM). Genetic deletion of myostatin or pharmacological inhibition with sActRIIB-Fc vs. Untreated KI mice / wild-type was evaluated on Muscle mass and function. Genetic and pharmacological inhibition of myostatin restored muscle mass in a mouse model of ADCNM, though pharmacological treatment did not improve muscle force or key pathological features.

synapsesocial.com/papers/6aa7afef79e9260bc85aac62https://doi.org/10.1002/jcsm.70338
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Myostatin inhibition promotes fast fibre hypertrophy but causes loss of AMP‐activated protein kinase signalling and poor exercise tolerance in a model of limb‐girdle muscular dystrophy R1/2A2020 · 14 citations
  2. 2Systemic Myostatin Inhibition via Liver-Targeted Gene Transfer in Normal and Dystrophic Mice2010 · 64 citations
  3. 3Pharmacological Inhibition of Myostatin in a Mouse Model of Typical Nemaline Myopathy Increases Muscle Size and Force2023 · 4 citations
  4. 4Changes in skeletal muscle and tendon structure and function following genetic inactivation of myostatin in rats2015 · 40 citations
  5. 5Clinical Applications of Myostatin Inhibitors for Neuromuscular Diseases2010 · 3 citations