PMID- 28694434
OWN - NLM
STAT- MEDLINE
DCOM- 20190115
LR  - 20190315
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Jul 10
TI  - Laquinimod treatment in the R6/2 mouse model.
PG  - 4947
LID - 10.1038/s41598-017-04990-1 [doi]
LID - 4947
AB  - The transgenic mouse model R6/2 exhibits Huntington's disease (HD)-like deficits 
      and basic pathophysiological similarities. We also used the pheochromocytoma-12 
      (PC12)-cell-line-model to investigate the effect of laquinimod on metabolic 
      activity. Laquinimod is an orally administered immunomodulatory substance 
      currently under development for the treatment of multiple sclerosis (MS) and HD. 
      As an essential effect, increased levels of BDNF were observed. Therefore, we 
      investigated the therapeutic efficacy of laquinimod in the R6/2 model, focusing 
      on its neuroprotective capacity. Weight course and survival were not influenced 
      by laquinimod. Neither were any metabolic effects seen in an inducible 
      PC12-cell-line model of HD. As a positive effect, motor functions of R6/2 mice at 
      the age of 12 weeks significantly improved. Preservation of morphologically 
      intact neurons was found after treatment in the striatum, as revealed by NeuN, 
      DARPP-32, and ubiquitin. Biochemical analysis showed a significant increase in 
      the brain-derived neurotrophic factor (BDNF) level in striatal but not in 
      cortical neurons. The number of mutant huntingtin (mhtt) and inducible nitric 
      oxide synthase (iNOS) positive cells was reduced in both the striatum and motor 
      cortex following treatment. These findings suggest that laquinimod could provide 
      a mild effect on motor function and striatal histopathology, but not on survival. 
      Besides influences on the immune system, influence on BDNF-dependent pathways in 
      HD are discussed.
FAU - Ellrichmann, Gisa
AU  - Ellrichmann G
AD  - Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, 
      Germany. gisa.ellrichmann@rub.de.
FAU - Blusch, Alina
AU  - Blusch A
AD  - Center of Clinical Research, Ruhr-University Bochum, Bochum, Germany.
FAU - Fatoba, Oluwaseun
AU  - Fatoba O
AD  - Center of Clinical Research, Ruhr-University Bochum, Bochum, Germany.
FAU - Brunner, Janine
AU  - Brunner J
AD  - Center of Clinical Research, Ruhr-University Bochum, Bochum, Germany.
FAU - Reick, Christiane
AU  - Reick C
AD  - Center of Clinical Research, Ruhr-University Bochum, Bochum, Germany.
FAU - Hayardeny, Liat
AU  - Hayardeny L
AD  - Galmed Pharmaceuticals, Tel Aviv, Israel.
AD  - Teva Pharmaceutical Industries Ltd, Tiqva, Israel.
FAU - Hayden, Michael
AU  - Hayden M
AD  - Teva Pharmaceutical Industries Ltd, Tiqva, Israel.
FAU - Sehr, Dominik
AU  - Sehr D
AD  - Department of Molecular Cell Biology, Institute of Biochemistry and 
      Pathobiochemistry, Ruhr-University Bochum, Bochum, Germany.
FAU - Winklhofer, Konstanze F
AU  - Winklhofer KF
AD  - Department of Molecular Cell Biology, Institute of Biochemistry and 
      Pathobiochemistry, Ruhr-University Bochum, Bochum, Germany.
FAU - Saft, Carsten
AU  - Saft C
AD  - Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, 
      Germany.
FAU - Gold, Ralf
AU  - Gold R
AD  - Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, 
      Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170710
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Biomarkers)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Quinolones)
RN  - 908SY76S4G (laquinimod)
SB  - IM
EIN - Sci Rep. 2019 Mar 15;9(1):4960. PMID: 30874566
MH  - Animals
MH  - Biomarkers
MH  - Body Weight
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - Cell Survival/drug effects
MH  - Disease Models, Animal
MH  - Energy Metabolism/drug effects
MH  - Fluorescent Antibody Technique
MH  - Gene Expression
MH  - Huntington Disease/drug therapy/etiology/metabolism/physiopathology
MH  - Mice
MH  - Mice, Transgenic
MH  - Motor Activity/drug effects
MH  - Neurons/drug effects/metabolism
MH  - PC12 Cells
MH  - Quinolones/*pharmacology
MH  - Rats
MH  - Survival Rate
PMC - PMC5504033
COIS- TEVA endorsed a professorship for C. Saft from 2007-2010. The Huntington Center, 
      Bochum received institutional compensations in the context of the LEGATO-HD 
      study. L. Hayardeny was, and M. Hayden is, an employee of TEVA Pharmaceutical 
      Industries Ltd, Israel.
EDAT- 2017/07/12 06:00
MHDA- 2019/01/16 06:00
PMCR- 2017/07/10
CRDT- 2017/07/12 06:00
PHST- 2017/02/01 00:00 [received]
PHST- 2017/05/23 00:00 [accepted]
PHST- 2017/07/12 06:00 [entrez]
PHST- 2017/07/12 06:00 [pubmed]
PHST- 2019/01/16 06:00 [medline]
PHST- 2017/07/10 00:00 [pmc-release]
AID - 10.1038/s41598-017-04990-1 [pii]
AID - 4990 [pii]
AID - 10.1038/s41598-017-04990-1 [doi]
PST - epublish
SO  - Sci Rep. 2017 Jul 10;7(1):4947. doi: 10.1038/s41598-017-04990-1.