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Comparative Study
. 2011 May;43(5):694-9.
doi: 10.1002/mus.21944. Epub 2011 Apr 1.

Soluble activin receptor type IIB increases forward pulling tension in the mdx mouse

C George Carlson  1 , Kay Bruemmer, Jenna Sesti, Casey Stefanski, Heather Curtis, Jeffrey Ucran, Jennifer Lachey, Jasbir S Seehra
Affiliations
Comparative Study

Soluble activin receptor type IIB increases forward pulling tension in the mdx mouse

C George Carlson et al. Muscle Nerve. 2011 May.

Abstract

Introduction: In this study we investigated the action of RAP-031, a soluble activin receptor type IIB (ActRIIB) comprised of a form of the ActRIIB extracellular domain linked to a murine Fc, and the NF-κB inhibitor, ursodeoxycholic acid (UDCA), on the whole body strength of mdx mice.

Methods: The whole body tension (WBT) method of assessing the forward pulling tension (FPT) exerted by dystrophic (mdx) mice was used.

Results: RAP-031 produced a 41% increase in body mass and a 42.5% increase in FPT without altering the FPT normalized for body mass (WBT). Coadministration of RAP-031 with UDCA produced increases in FPT that were associated with an increase in WBT.

Conclusions: Myostatin inhibition increases muscle mass without altering the fundamental weakness characteristic of dystrophic muscle. Cotreatment with an NF-κB inhibitor potentiates the effects of myostatin inhibition in improving FPT in mdx mice.

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Figures

Figure 1
Figure 1
RAP-031 treatment produces roughly proportional increases in body mass (A), FPT5 (B), and FPT10 (C) in young adult (30 day) mdx mice treated for 30 (A1, B1, C1), 60 (A2, B2, C2), or 90 days (A3, B3, C3). Black histobars – vehicle treated; grey histobars – RAP-031 treated. N represents the number of mdx mice in each group. *** - p< 0.001 in comparison to vehicle treated mdx mice.
Figure 2
Figure 2
RAP-031 treatment does not influence FPT normalized to body mass. (A1 to A3) WBT5 values at 30, 60, and 90 days, respectively. (B1 to B3) WBT10 values at 30, 60, and 90 days. (C1 to C3) FR values at 30, 60, and 90 days. Black histobars – vehicle treated; grey histobars – RAP-031 treated. N represents the number of mdx mice in each group. * - p< 0.05 in comparison to vehicle treated mdx mice. Note that the FR is significantly increased in the RAP-031 treated mice after 90 days of treatment.
Figure 3
Figure 3
The effect of RAP-031 treatment on the PDP at 30 (A1), 60 (A2), and 90 (A3) days. Black histobars – vehicle treated; grey histobars – RAP-031 treated. N represents the number of mdx mice in each group.
Figure 4
Figure 4
Combined RAP-031 and UDCA treatment for 30 days produced substantial increases in FPT and significant increases in WBT10. (A) Body weight, (B) FPT5, (C) FPT10, (D) WBT5, (E) WBT10, and (F) FR. Black histobars – vehicle treated, gray histobars – RAP-031 and UDCA treated. N is the number of mdx mice in each group. *, **, and *** indicates p< 0.05, p< 0.01, and p<0.001, respectively, in comparison to vehicle treated mice.
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References

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