Neural cell extracellular vesicles
Inventors
Stice, Steven L. • Webb, Robin Lynn • Stice, Tracey A.
Assignees
Aruna Bio Inc • University of Georgia Research Foundation Inc
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Publication Number
US-12139723-B2
Publication Date
2024-11-12
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 disease.
Core Innovation
The invention provides therapeutic pharmaceutical compositions comprising isolated extracellular vesicles (EVs) derived from non-transformed human neural progenitor cells that are capable of differentiating into neurons, astrocytes and oligodendrocytes in vitro. The EVs are produced from neural progenitor cells derived in vitro from pluripotent stem cells, or from neural cells derived in vitro from the neural progenitor cells or the pluripotent stem cells.
The EVs comprise one or more EV-associated molecules including 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). The described approach links the EV source and EV composition to inflammatory control in the brain context of the subject.
The described compositions are supported by neural EV/exosome sources derived from pluripotent-stem-cell-derived neural progenitor cells, including NPEX (hNP-derived neural EVs), as well as EVs derived from astrocytes (APEX) and mesenchymal stem cells (MSCEX). Protein cargo profiles are reported as unique protein sets in proteomics/mass spectrometry, and the EVs are characterized for uptake by differentiated neural cells and in vivo brain/stroke biodistribution after labeled EV injection.
Claims Coverage
The partial content includes one independent claim. The claim contains a core requirement of a method of reducing inflammation in the brain by administering a pharmaceutical composition comprising isolated EVs with specified source, differentiation capability, and EV-associated molecule cargo.
Inflammation-reducing brain EV pharmaceutical composition
A method of reducing inflammation in the brain of a subject by administering an effective amount of a pharmaceutical composition comprising isolated extracellular vesicles (EVs) derived from non-transformed human neural progenitor cells that are capable of differentiating into neurons, astrocytes and oligodendrocytes in vitro.
Pluripotent-stem-derived neural progenitor EV source
The EVs are produced from neural progenitor cells derived in vitro from pluripotent stem cells, or from neural cells derived in vitro from the neural progenitor cells or the pluripotent stem cells.
Defined EV-associated cargo molecules
The EVs comprise one or more of 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).
Across the independent claim, the central coverage is a brain inflammation reduction method using an effective amount of a pharmaceutical composition containing isolated EVs from non-transformed human neural progenitor cells with in vitro neuronal/astrocyte/oligodendrocyte differentiation capability, derived from pluripotent stem cells, and comprising specified EV-associated molecules (MCSP, PTX3, angiopoietin-1, IGFBP2, macrophage colony-stimulating factor, and NT5E).
Stated Advantages
Reduces inflammation in the brain of a subject.
Lowers the level of IL-17 in the subject [procedural detail omitted for safety].
Immune modulation is described, including increased Tregs and M2 macrophages and reduced inflammatory T-helper/IL-17 [procedural detail omitted for safety].
Improved functional outcomes in stroke models are described, including reduced infarct volume and improved survival/mortality and behavioral/motor outcomes [procedural detail omitted for safety].
MRI-detected reduced edema/swelling is described [procedural detail omitted for safety].
Documented Applications
Spinal cord injury, stroke, traumatic brain injury, and neurodegenerative disease are described as therapeutic contexts for neural EV/exosomes derived from pluripotent-stem-cell-derived neural progenitor cells [procedural detail omitted for safety].
Reduction of brain inflammation in a subject is described as a method use case [procedural detail omitted for safety].
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