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June 4, 2013Human Molecular Genetics28 citationsOpen Access

Cardiac -actin over-expression therapy in dominant ACTA1 disease

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Why the study?

Does transgenic over-expression of cardiac α-actin improve survival in mouse models of severe dominant ACTA1 disease?

Population

Mouse models of severe dominant ACTA1 disease (ACTA1(D286G). Acta1(+/-) mice and Acta1(H40Y) mice)

Comparison

Transgenic over-expression of cardiac α-actin in… vs Mice without the cardiac α-actin transgene

Design

Preclinical

Follow-up

Up to 5 months of age

Key result

Transgenic over-expression of cardiac α-actin reduced lethality before 30 days of age from ~59% to ~12% in the ACTA1(D286G) mouse model of dominant ACTA1 disease.

Authors

GRGianina RavenscroftEME. McNamaraLGLisa M. Griffiths

Discussion

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Member takes

Overview

May support α-actin augmentation in ACTA1 models; leaves open human translation and broader applicability.

Structured PICO

Does transgenic over-expression of cardiac α-actin improve survival in mouse models of severe dominant ACTA1 disease?

P
Population
Mouse models of severe dominant ACTA1 disease evaluated for survival up to 5 months of age.
I
Intervention
Transgenic over-expression of cardiac α-actin in postnatal skeletal muscle
C
Comparator
Mice without the cardiac α-actin transgene
O
Outcome
Survival/lethalityhard clinical

Cardiac α-actin over-expression reduces lethality in some, but not all, mouse models of dominant ACTA1 disease, suggesting potential therapeutic value.

Main Result

Absolute Event Rate: 12% vs 59%

Limitations

  • The reason cardiac α-actin was not effective in the Acta1(H40Y) mice is uncertain, possibly due to endogenously elevated levels of cardiac α-actin in skeletal muscles.
  • Acta1(H40Y) mice had endogenously elevated levels of cardiac α-actin in skeletal muscles, a finding not reported in dominant ACTA1 patients

Cite This Study

Ravenscroft et al. (2013) studied Dominant ACTA1 disease. Transgenic over-expression of cardiac α-actin vs. Control mice without the transgene was evaluated on Lethality before 30 days of age (in ACTA1(D286G) model). Transgenic over-expression of cardiac α-actin reduced lethality before 30 days of age from ~59% to ~12% in the ACTA1(D286G) mouse model of dominant ACTA1 disease.

synapsesocial.com/papers/6a963e8431394ac286fba94bhttps://doi.org/10.1093/hmg/ddt252
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