title: Intranasal Delivery of A Novel Amnion Cell Secretome Prevents Neuronal Damage and Preserves Function In A Mouse Multiple Sclerosis Model.
abstract: The ability of a novel intranasally delivered amnion cell derived biologic to suppress inflammation, prevent neuronal damage and preserve neurologic function in the experimental autoimmune encephalomyelitis animal model of multiple sclerosis was assessed. Currently, there are no existing optic nerve treatment methods for disease or trauma that result in permanent vision loss. Demyelinating optic nerve inflammation, termed optic neuritis, induces permanent visual dysfunction due to retinal ganglion cell damage in multiple sclerosis and experimental autoimmune encephalomyelitis. ST266, the biological secretome of Amnion-derived Multipotent Progenitor cells, contains multiple anti-inflammatory cytokines and growth factors. Intranasally administered ST266 accumulated in rodent eyes and optic nerves, attenuated visual dysfunction, and prevented retinal ganglion cell loss in experimental optic neuritis, with reduced inflammation and demyelination. Additionally, ST266 reduced retinal ganglion cell death in vitro. Neuroprotective effects involved oxidative stress reduction, SIRT1-mediated mitochondrial function promotion, and pAKT signaling. Intranasal delivery of neuroprotective ST266 is a potential novel, noninvasive therapeutic modality for the eyes, optic nerves and brain. The unique combination of biologic molecules in ST266 provides an innovative approach with broad implications for suppressing inflammation in autoimmune diseases, and for preventing neuronal damage in acute neuronal injury and chronic neurodegenerative diseases such as multiple sclerosis.
authors.affiliation: Scheie Eye Institute and FM Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Reas S
authors.initials: RS
authors.lastname: Khan
authors.affiliation: Scheie Eye Institute and FM Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Dine
authors.affiliation: School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Bailey
authors.initials: B
authors.lastname: Bauman
authors.affiliation: Drexel University School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Lorentsen
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Lin
authors.affiliation: Drexel University School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Helayna
authors.initials: H
authors.lastname: Brown
authors.affiliation: HealthPartners Institute, St. Paul, Minnesota, USA.
authors.forename: Leah R
authors.initials: LR
authors.lastname: Hanson
authors.affiliation: HealthPartners Institute, St. Paul, Minnesota, USA.
authors.forename: Aleta L
authors.initials: AL
authors.lastname: Svitak
authors.affiliation: Noveome Biotherapeutics, Inc., Pittsburgh, Pennsylvania, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Wessel
authors.affiliation: Noveome Biotherapeutics, Inc., Pittsburgh, Pennsylvania, USA.
authors.forename: Larry
authors.initials: L
authors.lastname: Brown
authors.affiliation: Scheie Eye Institute and FM Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Shindler
mesh_terms: D000281:Administration, Intranasal; D000650:Amnion / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism; D001685:Biological Factors / Q000008:administration & dosage*; D002470:Cell Survival / Q000187:drug effects; D003711:Demyelinating Diseases; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology; D009902:Optic Neuritis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D051381:Rats; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001685:Biological Factors; D018696:Neuroprotective Agents