PMID- 30829880
OWN - NLM
STAT- MEDLINE
DCOM- 20200612
LR  - 20200612
IS  - 1536-5166 (Electronic)
IS  - 1070-8022 (Print)
IS  - 1070-8022 (Linking)
VI  - 39
IP  - 2
DP  - 2019 Jun
TI  - Effects of Varying Intranasal Treatment Regimens in ST266-Mediated Retinal 
      Ganglion Cell Neuroprotection.
PG  - 191-199
LID - 10.1097/WNO.0000000000000760 [doi]
AB  - 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.
FAU - Khan, Reas S
AU  - Khan RS
AD  - 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.
FAU - Dine, Kimberly
AU  - Dine K
FAU - Wessel, Howard
AU  - Wessel H
FAU - Brown, Larry
AU  - Brown L
FAU - Shindler, Kenneth S
AU  - Shindler KS
LA  - eng
GR  - R01 EY019014/EY/NEI NIH HHS/United States
GR  - R43 EY015014/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Neuroophthalmol
JT  - Journal of neuro-ophthalmology : the official journal of the North American 
      Neuro-Ophthalmology Society
JID - 9431308
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Neuroprotective Agents)
SB  - IM
MH  - Administration, Intranasal
MH  - Amnion
MH  - Animals
MH  - Cell Survival/physiology
MH  - Disease Models, Animal
MH  - Encephalomyelitis, Autoimmune, Experimental/physiopathology
MH  - Female
MH  - Intercellular Signaling Peptides and Proteins/metabolism/*therapeutic use
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Multipotent Stem Cells/metabolism
MH  - Neuroprotection/drug effects
MH  - Neuroprotective Agents/metabolism/*therapeutic use
MH  - Nystagmus, Optokinetic/physiology
MH  - Optic Neuritis/physiopathology/*prevention & control
MH  - Retinal Diseases/physiopathology/*prevention & control
MH  - Retinal Ganglion Cells/*drug effects/physiology
MH  - Visual Acuity/physiology
PMC - PMC6522299
MID - NIHMS1517475
EDAT- 2019/03/05 06:00
MHDA- 2020/06/13 06:00
PMCR- 2020/06/01
CRDT- 2019/03/05 06:00
PHST- 2019/03/05 06:00 [pubmed]
PHST- 2020/06/13 06:00 [medline]
PHST- 2019/03/05 06:00 [entrez]
PHST- 2020/06/01 00:00 [pmc-release]
AID - 10.1097/WNO.0000000000000760 [doi]
PST - ppublish
SO  - J Neuroophthalmol. 2019 Jun;39(2):191-199. doi: 10.1097/WNO.0000000000000760.