Intranasal Delivery of A Novel Amnion Cell Secretome Prevents Neuronal Damage and Preserves Function In A Mouse Multiple Sclerosis Model.
| Autor: | Khan RS; Scheie Eye Institute and FM Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Dine K; Scheie Eye Institute and FM Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Bauman B; School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Lorentsen M; Drexel University School of Medicine, Philadelphia, Pennsylvania, USA., Lin L; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Brown H; Drexel University School of Medicine, Philadelphia, Pennsylvania, USA., Hanson LR; HealthPartners Institute, St. Paul, Minnesota, USA., Svitak AL; HealthPartners Institute, St. Paul, Minnesota, USA., Wessel H; Noveome Biotherapeutics, Inc., Pittsburgh, Pennsylvania, USA., Brown L; Noveome Biotherapeutics, Inc., Pittsburgh, Pennsylvania, USA., Shindler KS; Scheie Eye Institute and FM Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Scientific reports [Sci Rep] 2017 Jan 31; Vol. 7, pp. 41768. Date of Electronic Publication: 2017 Jan 31. |
| DOI: | 10.1038/srep41768 |
| Abstrakt: | 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. Competing Interests: HW and LB are full time employees of Noveome Biotherapeutics, Inc., which provided the ST266 product used in these studies. Noveome holds the following U.S. Patents: 8,088,732 and 8,741,646; the following foreign Patents: EP 1864132, JP 5017253, CN ZL200680019392.X, CA 2602684, CN ZL2008800110113.X; and has filed US Applications: 61/768,437, 14/183,780, 62/175,239, 15/180,855, 61/911,653, 61/911,660, 14/556,300; and International Application: PCT/US2016/37217 |
| Databáze: | MEDLINE |
| Externí odkaz: |
|