Using Extracellular Vesicles Released by GDNF-Transfected Macrophages for Therapy of Parkinson Disease

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  • Zhao, Yuling
    • Eshelman School of Pharmacy, Center for Nanotechnology in Drug Delivery
  • Haney, Matthew J.
    • Eshelman School of Pharmacy, Center for Nanotechnology in Drug Delivery
  • Fallon, John K.
    • Eshelman School of Pharmacy
  • Rodriguez, Myosotys
    • Other Affiliation: Florida International University
  • Swain, Carson J.
    • Eshelman School of Pharmacy
  • Arzt, Camryn J.
    • Eshelman School of Pharmacy
  • Smith, Philip C.
    • Eshelman School of Pharmacy
  • Loop, Matthew Shane
    • Eshelman School of Pharmacy
  • Harrison, Emily B.
    • Eshelman School of Pharmacy
  • El-Hage, Nazira
    • Other Affiliation: Florida International University
  • Batrakova, Elena V.
    • Eshelman School of Pharmacy, Center for Nanotechnology in Drug Delivery
Abstract
  • Extracellular vesicles (EVs) are cell-derived nanoparticles that facilitate transport of proteins, lipids, and genetic material, playing important roles in intracellular communication. They have remarkable potential as non-toxic and non-immunogenic nanocarriers for drug delivery to unreachable organs and tissues, in particular, the central nervous system (CNS). Herein, we developed a novel platform based on macrophage-derived EVs to treat Parkinson disease (PD). Specifically, we evaluated the therapeutic potential of EVs secreted by autologous macrophages that were transfected ex vivo to express glial-cell-line-derived neurotrophic factor (GDNF). EV-GDNF were collected from conditioned media of GDNF-transfected macrophages and characterized for GDNF content, size, charge, and expression of EV-specific proteins. The data revealed that, along with the encoded neurotrophic factor, EVs released by pre-transfected macrophages carry GDNF-encoding DNA. Four-month-old transgenic Parkin Q311(X)A mice were treated with EV-GDNF via intranasal administration, and the effect of this therapeutic intervention on locomotor functions was assessed over a year. Significant improvements in mobility, increases in neuronal survival, and decreases in neuroinflammation were found in PD mice treated with EV-GDNF. No offsite toxicity caused by EV-GDNF administration was detected. Overall, an EV-based approach can provide a versatile and potent therapeutic intervention for PD.
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  • Article
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  • In Copyright
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  • Attribution 3.0 United States
Journal title
  • Cells
Journal volume
  • 11
Journal issue
  • 12
Page start
  • 1933
Language
  • English
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  • Publisher
ISSN
  • 2073-4409

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