Chronic Dosing with Membrane Sealant Poloxamer 188 NF Improves Respiratory Dysfunction in Dystrophic Mdx and Mdx/Utrophin-/- Mice

PLoS One. 2015 Aug 6;10(8):e0134832. doi: 10.1371/journal.pone.0134832. eCollection 2015.


Poloxamer 188 NF (national formulary (NF) grade of P-188) improves cardiac muscle function in the mdx mouse and golden retriever muscular dystrophy models. However in vivo effects on skeletal muscle have not been reported. We postulated that P-188 NF might protect diaphragm muscle membranes from contraction-induced injury in mdx and mdx/utrophin-/- (dko) muscular dystrophy models. In the first study 7-month old mdx mice were treated for 22 weeks with subcutaneous (s.c.) injections of saline or P-188 NF at 3 mg/Kg. In the second, dkos were treated with saline or P-188 NF (1 mg/Kg) for 8 weeks beginning at age 3 weeks. Prednisone was the positive control in both studies. Respiratory function was monitored using unrestrained whole body plethysmography. P-188 NF treatment affected several respiratory parameters including tidal volume/BW and minute volume/BW in mdx mice. In the more severe dko model, P-188 NF (1 mg/Kg) significantly slowed the decline in multiple respiratory parameters compared with saline-treated dko mice. Prednisone's effects were similar to those seen with P-188 NF. Diaphragms from P-188 NF or prednisone treated mdx and dko mice showed signs of muscle fiber protection including less centralized nuclei, less variation in fiber size, greater fiber density, and exhibited a decreased amount of collagen deposition. P-188 NF at 3 mg/Kg s.c. also improved parameters of systolic and diastolic function in mdx mouse hearts. These results suggest that P-188 NF may be useful in treating respiratory and cardiac dysfunction, the leading causes of death in Duchenne muscular dystrophy patients.

Publication types

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

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Diaphragm / pathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Carriers / chemistry*
  • Half-Life
  • Heart / physiology
  • Hemodynamics / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred mdx
  • Mice, Knockout
  • Muscle Fibers, Skeletal / physiology
  • Muscular Dystrophy, Duchenne / drug therapy*
  • Muscular Dystrophy, Duchenne / physiopathology
  • Plethysmography
  • Poloxamer / administration & dosage*
  • Poloxamer / chemistry
  • Poloxamer / pharmacokinetics
  • Poloxamer / pharmacology
  • Prednisone / pharmacology
  • Prednisone / therapeutic use
  • Utrophin / deficiency
  • Utrophin / genetics*


  • Anti-Inflammatory Agents
  • Drug Carriers
  • Utrophin
  • Poloxamer
  • Prednisone