PMID- 29197515
OWN - NLM
STAT- MEDLINE
DCOM- 20190211
LR  - 20190215
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 130
DP  - 2018 Mar 1
TI  - Fingolimod anti-inflammatory and neuroprotective effects modulation of RAGE axis 
      in multiple sclerosis patients.
PG  - 71-76
LID - S0028-3908(17)30586-5 [pii]
LID - 10.1016/j.neuropharm.2017.11.047 [doi]
AB  - BACKGROUND: We investigated Fingolimod treatment effects on the RAGE (receptor 
      for advanced glycation endproducts) axis in multiple sclerosis (MS) patients. The 
      primary outcome of the study was whether Fingolimod treatment increases serum 
      levels of the soluble RAGE isoforms, sRAGE and esRAGE - both being considered 
      putative endogenous inhibitors of RAGE signaling. Additional variables were serum 
      levels of RAGE ligands, the high mobility group box (HMGB)1 and pentosidine. 
      METHODS: Serum levels of the study variables were measured by ELISA, and compared 
      between baseline (before Fingolimod treatment) and 6 and 12 months post-drug 
      treatment in 17 relapsing MS patients. Fingolimod treatment effects on MS disease 
      progression were assessed by comparing pre- and post-Fingolimod values of the 
      EDSS and rate of clinical relapse, and changes in the T1-and T2-enahncing lesions 
      on the MRI scan.methods RESULTS: Twelve months treatment with Fingolimod 
      increased serum levels of sRAGE and esRAGE by 32.4% (P = 0.004) and 48.5% 
      (P = 0.007) respectively. In addition, Fingolimod treatment reduced serum levels 
      of HMGB1 by 71.6% (P = 0.02) and pentosidine serum levels by 41.3% (P = 0.12). 
      EDSS remained stable (baseline: 3.57 +/- 1.56; post-Fingolimod: 3.54 +/- 1.2, 
      P = 0.96) and the rate of clinical relapse decreased near significantly 
      (P = 0.094). T1-and T2-enhancing lesions remained stable, showing no significant 
      changes pre-vs. post-Fingolimod treatment. CONCLUSION: Fingolimod mediates 
      modulation of the RAGE axis which apparently contributes to the Fingolimod's 
      anti-inflammatory and neuroprotective effects. These findings may provide a 
      rationale for the clinical efficacy of Fingolimod in pathological states other 
      than MS, where dysregulation of the RAGE axis plays a role.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Sternberg, Zohara
AU  - Sternberg Z
AD  - Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, 
      University at Buffalo, 100 High Street, Buffalo, NY, USA. Electronic address: 
      zs2@buffalo.edu.
FAU - Kolb, Channa
AU  - Kolb C
AD  - Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, 
      University at Buffalo, 100 High Street, Buffalo, NY, USA.
FAU - Chadha, Kailash
AU  - Chadha K
AD  - Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, 
      Buffalo, NY, USA.
FAU - Nir, Adam
AU  - Nir A
AD  - SBH Sciences, Natick MA, USA.
FAU - Nir, Raphael
AU  - Nir R
AD  - SBH Sciences, Natick MA, USA.
FAU - George, Rayan
AU  - George R
AD  - SBH Sciences, Natick MA, USA.
FAU - Johnson, Joseph
AU  - Johnson J
AD  - SBH Sciences, Natick MA, USA.
FAU - Yu, Jinhee
AU  - Yu J
AD  - Department of Biostatistics, State University of NY at Buffalo, Buffalo, NY, USA.
FAU - Hojnacki, David
AU  - Hojnacki D
AD  - Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, 
      University at Buffalo, 100 High Street, Buffalo, NY, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171129
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (HMGB1 Protein)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (esRAGE protein, human)
RN  - 0 (sRAGE protein, human)
RN  - 94ZLA3W45F (Arginine)
RN  - BJ4I2X2CQJ (pentosidine)
RN  - EC 2.7.11.22 (MOK protein, human)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - G926EC510T (Fingolimod Hydrochloride)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Adult
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Antigens, Neoplasm/*blood
MH  - Arginine/analogs & derivatives/blood
MH  - Female
MH  - Fingolimod Hydrochloride/*therapeutic use
MH  - HMGB1 Protein/blood
MH  - Humans
MH  - Lysine/analogs & derivatives/blood
MH  - Male
MH  - Middle Aged
MH  - Mitogen-Activated Protein Kinases/*blood
MH  - Multiple Sclerosis/blood/*drug therapy
MH  - Neuroprotective Agents/*therapeutic use
MH  - Receptor for Advanced Glycation End Products/blood
MH  - Young Adult
OTO - NOTNLM
OT  - Acute phase protein
OT  - Immune suppression
OT  - Inflammation
OT  - Ligands
OT  - Neuroprotection
OT  - Soluble RAGE isoforms
EDAT- 2017/12/05 06:00
MHDA- 2019/02/12 06:00
CRDT- 2017/12/04 06:00
PHST- 2016/11/16 00:00 [received]
PHST- 2017/09/14 00:00 [revised]
PHST- 2017/11/27 00:00 [accepted]
PHST- 2017/12/05 06:00 [pubmed]
PHST- 2019/02/12 06:00 [medline]
PHST- 2017/12/04 06:00 [entrez]
AID - S0028-3908(17)30586-5 [pii]
AID - 10.1016/j.neuropharm.2017.11.047 [doi]
PST - ppublish
SO  - Neuropharmacology. 2018 Mar 1;130:71-76. doi: 10.1016/j.neuropharm.2017.11.047. 
      Epub 2017 Nov 29.