Advancing treatment of spinal muscular atrophy through inhibition of the myostatin signaling pathway

  • Expert Rev Neurother. 2026 Mar;26(3):211-225. doi: 10.1080/14737175.2026.2621405.
Richard S Finkel  1 ,  Thomas O Crawford  2 ,  Basil T Darras  3 ,  Thomas Brown  4 ,  Mouhamed Gueye  4 ,  Mary Schroth  5 ,  Jena M Krueger  6 ,  Laurent Servais  7  8
Affiliations
  • 1. Center for Experimental Neurotherapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • 2. Johns Hopkins Neurology, Johns Hopkins Medicine, Baltimore, MD, USA.
  • 3. Department of Neurology, Neuromuscular Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
  • 4. Scholar Rock, Inc., Cambridge, MA, USA.
  • 5. School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
  • 6. Department of Neurology, Helen DeVos Children's Hospital at Spectrum Health, Grand Rapids, MI, USA.
  • 7. Department of Paediatrics, MDUK Oxford Neuromuscular Centre and NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
  • 8. Department of Paediatrics, Neuromuscular Reference Centre, University Hospital of Liège, Liège, Belgium.
PMID: 41566720 DOI: 10.1080/14737175.2026.2621405
Abstract

Introduction: In spinal muscular atrophy (SMA), irreversible loss of spinal motor neurons and progressive skeletal muscle atrophy cause continuous weakness and loss of motor function. Treatments that increase levels of survival motor neuron (SMN) protein in motor neurons have greatly improved prognoses for patients, but significant unmet needs remain. Myostatin is a protein secreted by skeletal muscle that acts as a negative regulator of muscle growth. Inhibition of the myostatin signaling pathway may improve motor function in SMA and Other neuromuscular diseases.

Areas covered: This article reviews the role of muscle in SMA and the potential for treatments that inhibit the myostatin signaling pathway in neuromuscular diseases. Preclinical and clinical trial data are discussed for these muscle-targeted treatments in development for SMA.

Expert opinion: SMN-targeted disease-modifying treatments focus on motor neuron survival rather than muscle. Treated individuals nonetheless experience a range of persistent muscle weakness. Treatments that inhibit myostatin signaling represent a potential complementary pathway for direct muscle enhancement. In the evolving SMA treatment landscape, understanding how muscle-targeted treatment can be incorporated into clinical practice will facilitate individualized treatment decisions and identify outcomes that best encapsulate maintenance or improvement of motor function across the phenotypic spectrum of SMA.

Keywords
Apitegromab; emugrobart; motor function; muscle atrophy; myostatin; neuromuscular; spinal muscular atrophy; taldefgrobep alfa.
Products