Rapamycin nanoparticles target defective autophagy in muscular dystrophy to enhance both strength and cardiac function

Kristin P. Bibee, Ya Jian Cheng, James K. Ching, Jon N. Marsh, Allison J. Li, Richard M. Keeling, Anne M. Connolly, Paul T. Golumbek, Jacob W. Myerson, Grace Hu, Junjie Chen, William D. Shannon, Gregory M. Lanza, Conrad C. Weihl, Samuel A. Wickline

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Duchenne muscular dystrophy in boys progresses rapidly to severe impairment of muscle function and death in the second or third decade of life. Current supportive therapy with corticosteroids results in a modest increase in strength as a consequence of a general reduction in inflammation, albeit with potential untoward long-term side effects and ultimate failure of the agent to maintain strength. Here, we demonstrate that alternative approaches that rescue defective autophagy in mdx mice, a model of Duchenne muscular dystrophy, with the use of rapamycin-loaded nanoparticles induce a reproducible increase in both skeletal muscle strength and cardiac contractile performance that is not achievable with conventional oral rapamycin, even in pharmacological doses. This increase in physical performance occurs in both young and adult mice, and, surprisingly, even in aged wildtype mice, which sets the stage for consideration of systemic therapies to facilitate improved cell function by autophagic disposal of toxic byproducts of cell death and regeneration.

Original languageEnglish (US)
Pages (from-to)2047-2061
Number of pages15
JournalFASEB Journal
Issue number5
StatePublished - May 2014
Externally publishedYes


  • Cardiomyopathy
  • Drug delivery
  • Duchenne
  • Nanomedicine
  • Perfluorocarbon

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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