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July 13, 2020The Journal of Physiology

Genetic inhibition of myostatin resulted in a 1.5- to 2-fold increase in muscle mass but did not improve muscle strength and exacerbated exercise intolerance, with similar functional results for pharmacological inhibition.

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Why the study?

Limb-girdle muscular dystrophy R1 has no available therapies, and whether induction of muscle growth via myostatin inhibition represents a viable therapeutic strategy was unknown.

Does myostatin inhibition improve muscle strength and exercise tolerance in a mouse model of limb-girdle muscular dystrophy R1?

Population

Mouse model of LGMD R1 (C3KO mice)

Comparison

Genetic (follistatin overexpression) or pharmacological (anti-myostatin antibody) myostatin inhibition vs control C3KO

Authors

IKIrina KramerovaMMMasha MarinovJOJane Owens

Discussion

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Overview

Myostatin inhibition unlikely to benefit LGMD R1; leaves open context-specific effects in other dystrophies.

Structured PICO

Does myostatin inhibition improve muscle strength and exercise tolerance in a mouse model of limb-girdle muscular dystrophy R1?

P
Population
Mouse model of limb-girdle muscular dystrophy R1 (LGMD R1) using CAPN3 knockout mice (C3KO)
I
Intervention
Genetic inhibition of myostatin (overexpression of follistatin) or pharmacological inhibition (anti-myostatin antibody)
C
Comparator
Untreated C3KO mice
O
Outcome
Muscle mass, muscle strength, and exercise tolerancesurrogate

Myostatin inhibition increases muscle mass but impairs oxidative capacity and exercise tolerance in a mouse model of LGMD R1, indicating it is unlikely to be a viable therapeutic strategy.

Cite This Study

Kramerova et al. (2020) studied this question.

synapsesocial.com/papers/6a90ebe91a4f16208192cff2https://doi.org/10.1113/jp279943
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Also Consider

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

  1. 1Genetic and Pharmacologic Inhibition of Myostatin Restores Muscle Mass in a Dynamin 2 ‐Related Centronuclear Myopathy Mouse Model2026
  2. 2Muscle hypertrophy induced by myostatin inhibition accelerates degeneration in dysferlinopathy2015 · 42 citations
  3. 3Clinical Applications of Myostatin Inhibitors for Neuromuscular Diseases2010 · 3 citations
  4. 4Myostatin Mutation Associated with Gross Muscle Hypertrophy in a Child2004 · 1,403 citations
  5. 5Downregulation of myostatin pathway in neuromuscular diseases may explain challenges of anti-myostatin therapeutic approaches2017 · 139 citations