# ACE-031 Study



## TwisT (Jun 12, 2011)

Acceleron Pharma Inc., 128 Sidney St., Cambridge, MA 02139, USA.
*Abstract*

This  is the first report that inhibition of negative regulators of skeletal  muscle by a soluble form of activin type IIB receptor (ACE-031)  increases muscle mass independent of fiber-type expression. This finding  is distinct from the effects of selective pharmacological inhibition of  myostatin (GDF-8), which predominantly targets type II fibers. In our  study 8-wk-old C57BL/6 mice were treated with ACE-031 or vehicle control  for 28 days. By the end of treatment, *mean body weight of the ACE-031  group was 16% greater than that of the control group, and wet weights of  soleus, plantaris, gastrocnemius, and extensor digitorum longus muscles  increased by 33, 44, 46 and 26%*, respectively (P<0.05). Soleus  fiber-type distribution was unchanged with ACE-031 administration, and  *mean fiber cross-sectional area increased by 22 and 28%* (P<0.05) in  type I and II fibers, respectively. In the plantaris, a predominantly  type II fiber muscle, *mean fiber cross-sectional area increased by 57%  with ACE-031 treatment*. Analysis of myosin heavy chain (MHC) isoform  transcripts by real-time PCR indicated no change in transcript levels in  the soleus, but a decline in MHC I and IIa in the plantaris. In  contrast, electrophoretic separation of total soleus and plantaris  protein indicated that there was no change in the proportion of MHC  isoforms in either muscle. Thus these data provide optimism that ACE-031  may be a viable therapeutic in the treatment of musculoskeletal  diseases. Future studies should be undertaken to confirm that the  observed effects are not age dependent or due to the relatively short  study duration.


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