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July 23, 2015Human Molecular GeneticsOpen Access

Myostatin inhibition in dysferlin-deficient mice initially improved histopathology but ultimately exacerbated muscle degeneration and increased serum CK levels.

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Why the study?

Does myostatin inhibition accelerate muscle degeneration in dysferlin-deficient mice?

Population

Dysferlin-deficient (Dysf(-/-)) mice and dystrophin-deficient (mdx) mice

Design

Preclinical

Key result

Myostatin inhibition in dysferlin-deficient mice initially improved histopathology but ultimately exacerbated muscle degeneration and increased serum CK levels.

Authors

YLYun‐Sil LeeALAdam LeharSSSuzanne M. Sebald

Discussion

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Overview

Myostatin inhibition may exacerbate degeneration in dysferlin-deficient models; leaves open safety in human muscular dystrophies.

Structured PICO

Does myostatin inhibition accelerate muscle degeneration in dysferlin-deficient mice?

P
Population
Dysferlin-deficient (Dysf(-/-)) mice and dystrophin-deficient (mdx) mice used to investigate the effects of blocking the myostatin pathway.
I
Intervention
Myostatin inhibition via transgenic expression of follistatin in skeletal muscle or systemic administration of soluble activin type IIB receptor (ACVR2B/Fc)
O
Outcome
Muscle degeneration, histopathology, muscle mass, fibrotic changes, and serum CK levelssurrogate

Inducing muscle hypertrophy by myostatin blockade in dysferlin-deficient mice exacerbates muscle degeneration, highlighting potential detrimental effects in specific muscular dystrophies.

Cite This Study

Lee et al. (2015) studied Dysferlinopathy. Myostatin inhibition (follistatin transgene expression or ACVR2B/Fc) was evaluated on Muscle degeneration and histopathology. Myostatin inhibition in dysferlin-deficient mice initially improved histopathology but ultimately exacerbated muscle degeneration and increased serum CK levels.

synapsesocial.com/papers/6a402601901a52dbcb71c584https://doi.org/10.1093/hmg/ddv288
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Also Consider

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  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. 2Myostatin propeptide‐mediated amelioration of dystrophic pathophysiology2005 · 241 citations
  3. 3Myostatin Mutation Associated with Gross Muscle Hypertrophy in a Child2004 · 1,405 citations
  4. 4Downregulation of myostatin pathway in neuromuscular diseases may explain challenges of anti-myostatin therapeutic approaches2017 · 139 citations
  5. 5Inhibition of myostatin with emphasis on follistatin as a therapy for muscle disease2009 · 191 citations