Gene therapy for overexpressing Neuregulin 1 type I in skeletal muscles promotes functional improvement in the SOD1G93A ALS mice

Guillem Mòdol-Caballero, Mireia Herrando-Grabulosa, Belén García-Lareu, Neus Solanes, Sergi Verdés, Rosario Osta, Isaac Francos-Quijorna, Rubèn López-Vales, Ana Cristina Calvo, Assumpció Bosch*, Xavier Navarro

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)


Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motoneurons (MNs), with no effective treatment currently available. The molecular mechanisms that are involved in MN death are complex and not fully understood, with partial contributions of surrounding glial cells and skeletal muscle to the disease. Neuregulin 1 (NRG1) is a trophic factor highly expressed in MNs and neuromuscular junctions. Recent studies have suggested a crucial role of the isoform I (NRG1-I) in the collateral reinnervation process in skeletal muscle, and NRG1-III in the preservation of MNs in the spinal cord, opening a window for developing novel therapies for neuromuscular diseases like ALS. In this study, we overexpressed NRG1-I widely in the skeletal muscles of the SOD1G93A transgenic mouse. The results show that NRG1 gene therapy activated the survival pathways in muscle and spinal cord, increasing the number of surviving MNs and neuromuscular junctions and reducing the astroglial reactivity in the spinal cord of the treated SOD1G93A mice. Furthermore, NRG1-I overexpression preserved motor function and delayed the onset of clinical disease. In summary, our data indicates that NRG1 plays an important role on MN survival and muscle innervation in ALS, and that viral-mediated overexpression of NRG1 isoforms may be considered as a promising approach for ALS treatment.

Original languageAmerican English
Article number104793
JournalNeurobiology of Disease
Publication statusPublished - Apr 2020


  • Amyotrophic lateral sclerosis
  • ErbB receptors
  • Motoneuron
  • Motor function
  • Neuregulin 1
  • Neuromuscular junction
  • Spinal cord


Dive into the research topics of 'Gene therapy for overexpressing Neuregulin 1 type I in skeletal muscles promotes functional improvement in the SOD1<sup>G93A</sup> ALS mice'. Together they form a unique fingerprint.

Cite this