Intranasal Delivery of A Novel Amnion Cell Secretome Prevents Neuronal Damage and Preserves Function In A Mouse Multiple Sclerosis Model

Reas S Khan,Aleta L Svitak,Michael Lorentsen,Lisa Lin,Kenneth S Shindler,Helayna Brown,Larry Brown,Howard Wessel,Bailey Bauman,Leah R Hanson,Kimberly Dine

doi:10.1038/srep41768

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.

Highlights

Other lesions throughout the central nervous system (CNS) white matter in multiple sclerosis patients
To determine if intranasal delivery could target the tissues of the eye, the biodistribution of ST266 labeled with I-12526 was examined in anesthetized rats. [I-125]ST266 administered via the intranasal route in rats reached the CNS within 30 minutes, and was detected in the vitreous and the optic nerve at markedly higher concentrations than in the brain (Fig. 1)
The current results demonstrate that intranasally delivered ST266 accumulated at therapeutic levels in optic nerve and in the vitreous, such that it reduced loss of RGCs and preserved RGC function in experimental optic neuritis

Summary

Introduction

Other lesions throughout the central nervous system (CNS) white matter in multiple sclerosis patients. The neurological repair potential of amnion epithelial cells has been shown to reduce fetal brain injury in response to intrauterine inflammation[10]. The AMP cell secretome called ST266 (formerly Amnion-derived Cellular Cytokine Solution[18]; ACCS) has been shown to enhance wound healing[19], promote macrophage activity[20], and exhibit both anti-inflammatory and neuroprotective properties in the treatment of a penetrating ballistic brain injury model[21,22]. The potential ability of the amnion cell derived ST266 secretome to reduce inflammation and prevent neuronal loss was examined in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis

Methods

Results

Conclusion