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).
Researchers at the University of North Carolina at Chapel Hill have developed a novel platform based on macrophage-derived EVs to treat Parkinson’s disease (PD). Specifically, they 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.
Transgenic mice (4 mo. old) were intranasally injected with: saline (10 µL/mouse), or (3) EV-GDNF (3×109 particles/10 µL/mouse), or sham EVs (3×109 particles/10 µL/mouse). Wild type control mice were intranasally injected with saline (10 µL/mouse). Animals were sacrificed at mo. 16, brain slides were stained with Nissl staining (A – D) and H&E staining (E –H). The obtained bright light images show lower number of Nissl bodies with neuronal shrinkage (B) and damages tissues with degeneration in the neurons (F) in PD mice treated with saline when compared to WT mice (A, E). Histological analysis indicate neuroprotective effects in the brain of PD mice treated with EV-GDNF with healthy morphology in tissue structure and high integrity of neurons (C, G) when comparted to PD mice treated with saline (B, F). The administration of sham EVs did not have significant therapeutic effect in PD mice (D, H). Black arrows, degenerated neurons; blue arrows, elongated irregular nuclear morphology.