Laminin-111 protein therapy enhances muscle regeneration and repair in the GRMD dog model of Duchenne muscular dystrophy

Hum Mol Genet. 2019 Aug 15;28(16):2686-2695. doi: 10.1093/hmg/ddz086.

Abstract

Duchenne muscular dystrophy (DMD) is a devastating X-linked disease affecting ~1 in 5000 males. DMD patients exhibit progressive muscle degeneration and weakness, leading to loss of ambulation and premature death from cardiopulmonary failure. We previously reported that mouse Laminin-111 (msLam-111) protein could reduce muscle pathology and improve muscle function in the mdx mouse model for DMD. In this study, we examined the ability of msLam-111 to prevent muscle disease progression in the golden retriever muscular dystrophy (GRMD) dog model of DMD. The msLam-111 protein was injected into the cranial tibial muscle compartment of GRMD dogs and muscle strength and pathology were assessed. The results showed that msLam-111 treatment increased muscle fiber regeneration and repair with improved muscle strength and reduced muscle fibrosis in the GRMD model. Together, these findings support the idea that Laminin-111 could serve as a novel protein therapy for the treatment of DMD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Disease Models, Animal
  • Dogs
  • Laminin / administration & dosage
  • Laminin / pharmacology*
  • Male
  • Mice
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Muscular Dystrophy, Duchenne / diagnosis
  • Muscular Dystrophy, Duchenne / etiology
  • Muscular Dystrophy, Duchenne / physiopathology*
  • Muscular Dystrophy, Duchenne / therapy*
  • Phenotype
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacology*
  • Regeneration / drug effects*
  • Treatment Outcome

Substances

  • Biomarkers
  • Laminin
  • Recombinant Proteins