Neural cell extracellular vesicles
Inventors
Stice, Steven L. • Webb, Robin Lynn • Stice, Tracy A.
Assignees
Aruna Bio Inc • University of Georgia Research Foundation Inc
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Publication Number
US-11993787-B2
Publication Date
2024-05-28
Expiration Date
Abstract
Disclosed herein are neural extracellular vesicles (EVs) and methods of using these EVs in the treatment of spinal cord injury, stroke, and traumatic brain injury and neurodegenerative diseases.
Core Innovation
Neural extracellular vesicles (EVs), including EVs/exosomes produced from neural progenitors derived from pluripotent stem cells, differentiated neural/glial cells, and other neural-lineage sources, are presented for therapeutic treatment of spinal cord injury, stroke, traumatic brain injury, and neurodegenerative diseases. The document describes that the neural EVs are formulated as pharmaceutical compositions that include a therapeutically effective amount of EVs and a pharmaceutically acceptable carrier.
The disclosed EVs are characterized and shown to include structural features such as multivesicular bodies (MVBs), and they exhibit nanoparticle tracking size distribution with a size peak around 55 nm and a size range of about 25–250 nm. The document further describes EV uptake by differentiated neural cells, including uptake studies using DiI labeling, and presents functional neuroprotection in vitro under starvation stress.
The document also describes in vivo efficacy and biodistribution across rodent and large-animal stroke models, including reductions in MRI lesion/infarct volume and improvements in mortality/survival and neurobehavioral and motor outcomes. Immune modulation is described, including increased regulatory T cells and M2 macrophages, and the document includes EV composition and biomarker profiling comparisons among neural EV products (NPEX/APEX/MSCEX), including proteomic uniqueness and the presence or absence of FGF2 depending on the culture media.
Claims Coverage
The partial content provides one independent claim. The claim contains 3 main inventive elements: a pharmaceutical composition including therapeutically effective EVs from non-transformed human neural progenitor cells with specified in vitro differentiation capability; EVs comprising a specific set of marker components; and EVs that also include an exogenous agent selected from a defined group, with a pharmaceutically acceptable carrier.
Pharmaceutical composition with neural progenitor-derived EVs
A pharmaceutical composition comprising a therapeutically effective amount of extracellular vesicles (EVs) obtained from non-transformed human neural progenitor cells that are capable of differentiating into neurons, astrocytes and oligodendrocytes in vitro, and a pharmaceutically acceptable carrier.
EVs comprising specified protein markers
The EVs comprise melanoma-associated chondroitin sulfate proteoglycan (MCSP), pentraxin-3 (PTX3), angiopoietin-1, insulin-like growth factor-binding protein 2 (IGFBP2), macrophage colony-stimulating factor, and ecto-5′-nucleotidase (NT5E).
EVs with an exogenous agent selected from a defined group
The EVs comprise an exogenous agent selected from the group consisting of an siRNA, an antisense oligonucleotide, a peptide, a protein, an antibody, and a small molecule.
Overall, the independent claim is directed to a pharmaceutical composition that delivers neural progenitor cell-derived EVs from non-transformed human neural progenitors, where the EVs contain a defined set of marker components and carry an exogenous agent chosen from a specified list.
Stated Advantages
Documented Applications
Therapeutic treatment of spinal cord injury.
Therapeutic treatment of stroke.
Therapeutic treatment of traumatic brain injury.
Therapeutic treatment of neurodegenerative diseases.
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