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Effects of Varying Intranasal Treatment Regimens in ST266-Mediated Retinal Ganglion Cell Neuroprotection

Khan, Reas S., PhD; Dine, Kimberly, BS; Wessel, Howard, BS, MBA; Brown, Larry, ScD; Shindler, Kenneth S., MD, PhD

Section Editor(s): L. Bennett, Jeffrey MD, PhD; Shindler, Kenneth S. MD, PhD

Journal of Neuro-Ophthalmology: June 2019 - Volume 39 - Issue 2 - p 191–199
doi: 10.1097/WNO.0000000000000760
Basic and Translational Research: Bench to Bedside

Introduction: Previous studies have shown that intranasally administered ST266, a novel biological secretome of amnion‐derived multipotent progenitor cells containing multiple growth factors and anti-inflammatory cytokines, attenuated visual dysfunction and prevented retinal ganglion cell (RGC) loss in experimental optic neuritis. Long-term effects and dose escalation studies examined here have not been reported previously.

Methods: Optic neuritis was induced in the multiple sclerosis model experimental autoimmune encephalomyelitis (EAE). EAE and control mice were treated once or twice daily with intranasal placebo/vehicle or ST266 beginning after onset of optic neuritis for either 15 days or continuously until sacrifice. Visual function was assessed by optokinetic responses (OKRs). RGC survival and optic nerve inflammation and demyelination were measured.

Results: Both once and twice daily continuous intranasal ST266 treatment from disease onset to 56 days after EAE induction significantly increased OKR scores, decreased RGC loss, and reduced optic nerve inflammation and demyelination compared with placebo (saline, nonspecific protein solution, or cell culture media)-treated EAE mice. ST266 treatment given for just 15 days after disease onset, then discontinued, only delayed OKR decreases, and had limited effects on RGC survival and optic nerve inflammation 56 days after disease induction.

Conclusions: ST266 is a potential neuroprotective therapy to prevent RGC damage, and intranasal delivery warrants further study as a novel mechanism to deliver protein therapies for optic neuropathies. Results suggest that once daily ST266 treatment is sufficient to sustain maximal benefits and demonstrate that neuroprotective effects promoted by ST266 are specific to the combination of factors present in this complex biologic therapy.

Scheie Eye Institute (RSK, KD, KSS), FM Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania; and Noveome Biotherapeutics, Inc. (HW, LB), Pittsburgh, Pennsylvania.

Address correspondence to Kenneth S. Shindler, MD, PhD, FM Kirby Center for Molecular Ophthalmology, Stellar-Chance Laboratories, 3rd Floor, 422 Curie Boulevard, Philadelphia, PA 19104; E-mail:

Supported by NIH grant EY015014, Research to Prevent Blindness, and the FM Kirby Foundation. Portions of this work were subcontracted from grants to Noveome Biotherapeutics, Inc., through US Navy Contract # N62645-13-C-4014, Cell-Based Wound Therapeutics for Combat Casualties and The State of Pennsylvania, 2014 Bio-Technology Grant SAP#4100068500.

H. Wessel and L. Brown are full-time employees of Noveome Biotherapeutics, Inc., which provided the ST266 product used in these studies. K. S. Shindler received research funding and has received consulting fees for discussions of clinical needs for optic neuritis from Noveome.

© 2019 by North American Neuro-Ophthalmology Society