A soluble activin type IIB receptor improves function in a mouse model of amyotrophic lateral sclerosis

Brett M. Morrison, Jennifer L. Lachey, Leigh C. Warsing, Beverlie L. Ting, Abigail E. Pullen, Kathryn W. Underwood, Ravindra Kumar, Dianne Sako, Asya Grinberg, Vicki Wong, Elizabeth Colantuoni, Jasbir S. Seehra, Kathryn R. Wagner

Research output: Contribution to journalArticlepeer-review


Amyotrophic lateral sclerosis (ALS) is a neurologic disease characterized by progressive weakness that results in death within a few years of onset by respiratory failure. Myostatin is a member of the TGF-β superfamily that is predominantly expressed in muscle and acts as a negative regulator of muscle growth. Attenuating myostatin has previously been shown to produce increased muscle mass and strength in normal and disease animal models. In this study, a mouse model of ALS (SOD1G93A transgenic mice) was treated with a soluble activin receptor, type IIB (ActRIIB.mFc) which is a putative endogenous signaling receptor for myostatin in addition to other ligands of the TGF-β superfamily. ActRIIB.mFc treatment produces a delay in the onset of weakness, an increase in body weight and grip strength, and an enlargement of muscle size whether initiated pre-symptomatically or after symptom onset. Treatment with ActRIIB.mFc did not increase survival or neuromuscular junction innervation in SOD1G93A transgenic mice. Pharmacologic treatment with ActRIIB.mFc was superior in all measurements to genetic deletion of myostatin in SOD1G93A transgenic mice. The improved function of SOD1G93A transgenic mice following treatment with ActRIIB.mFc is encouraging for the development of TGF-β pathway inhibitors to increase muscle strength in patients with ALS.

Original languageEnglish (US)
Pages (from-to)258-268
Number of pages11
JournalExperimental Neurology
Issue number2
StatePublished - Jun 2009


  • ALS
  • Activin receptor
  • Muscle
  • Myostatin
  • SOD1
  • Treatment

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience


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