PMID- 28823953
OWN - NLM
STAT- MEDLINE
DCOM- 20180522
LR  - 20181113
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 1673
DP  - 2017 Oct 15
TI  - Beneficial effects of glatiramer acetate in Huntington's disease mouse models: 
      Evidence for BDNF-elevating and immunomodulatory mechanisms.
PG  - 102-110
LID - S0006-8993(17)30349-9 [pii]
LID - 10.1016/j.brainres.2017.08.013 [doi]
AB  - Huntington's disease (HD) is a fatal, neurodegenerative movement disorder that 
      has no cure and few treatment options. In these preclinical studies, we tested 
      the effects of chronic treatment of glatiramer acetate (GA; Copaxone(R)), an 
      FDA-approved drug used as first-line therapy for MS, in two different HD mouse 
      models, and explored potential mechanisms of action of drug efficacy. Groups of 
      CAG140 knock-in and N171-82Q transgenic mice were treated with GA for up to 1year 
      of age (CAG140 knock-in mice) or 20weeks (N171-82Q mice). Various behavioral 
      assays were measured over the course of drug treatment whereby GA treatment 
      delayed the onset and reduced the severity of HD behavioral symptoms in both 
      mouse models. The beneficial actions of GA were associated with elevated levels 
      of promoter I- and IV-driven brain-derived neurotrophic factor (Bdnf) expression 
      and reduced levels of cytokines, in particular, interleukins IL4 and IL12, in the 
      brains of HD mice. In addition, the GA-induced effects on BDNF, IL4 and IL12 
      levels were detected in plasma from drug-treated mice and rats, suggesting 
      utility as a peripheral biomarker of treatment effectiveness. These preclinical 
      studies support the use of GA as a relevant clinical therapy for HD patients.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Corey-Bloom, Jody
AU  - Corey-Bloom J
AD  - Department of Neurosciences, University of California, San Diego, CA, USA.
FAU - Aikin, Alaina M
AU  - Aikin AM
AD  - Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.
FAU - Gutierrez, Ashley M
AU  - Gutierrez AM
AD  - Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.
FAU - Nadhem, Jwan S
AU  - Nadhem JS
AD  - Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.
FAU - Howell, Taylor L
AU  - Howell TL
AD  - Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.
FAU - Thomas, Elizabeth A
AU  - Thomas EA
AD  - Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA. 
      Electronic address: bthomas@scripps.edu.
LA  - eng
GR  - R21 NS087986/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20170818
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neuroprotective Agents)
RN  - 187348-17-0 (Interleukin-12)
RN  - 207137-56-2 (Interleukin-4)
RN  - 5M691HL4BO (Glatiramer Acetate)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cerebral Cortex/drug effects/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression/drug effects
MH  - Glatiramer Acetate/*pharmacology
MH  - Huntington Disease/*drug therapy/*metabolism
MH  - Interleukin-12/metabolism
MH  - Interleukin-4/metabolism
MH  - Male
MH  - Mice, Transgenic
MH  - Motor Activity/drug effects/physiology
MH  - Neuroprotective Agents/*pharmacology
MH  - Random Allocation
MH  - Rats, Sprague-Dawley
PMC - PMC5595665
MID - NIHMS901206
OTO - NOTNLM
OT  - Huntingtin
OT  - Striatum
OT  - Therapeutic
EDAT- 2017/08/22 06:00
MHDA- 2018/05/23 06:00
PMCR- 2018/10/15
CRDT- 2017/08/22 06:00
PHST- 2017/06/15 00:00 [received]
PHST- 2017/08/08 00:00 [revised]
PHST- 2017/08/11 00:00 [accepted]
PHST- 2017/08/22 06:00 [pubmed]
PHST- 2018/05/23 06:00 [medline]
PHST- 2017/08/22 06:00 [entrez]
PHST- 2018/10/15 00:00 [pmc-release]
AID - S0006-8993(17)30349-9 [pii]
AID - 10.1016/j.brainres.2017.08.013 [doi]
PST - ppublish
SO  - Brain Res. 2017 Oct 15;1673:102-110. doi: 10.1016/j.brainres.2017.08.013. Epub 
      2017 Aug 18.