Glucagon-like peptide-1 analog, Liraglutide, delays onset of experimental autoimmune encephalitis in Lewis rats
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Glucagon-like peptide-1 analog, Liraglutide, delays onset of experimental autoimmune encephalitis in Lewis rats. / Della Valle, Brian William; Brix, Gitte S.; Brock, Birgitte; Gejl, Michael; Landau, Anne M.; Moller, Arne; Rungby, Jorgen; Larsen, Agnete.
In: Frontiers in Pharmacology, Vol. 7, 433, 18.11.2016.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Glucagon-like peptide-1 analog, Liraglutide, delays onset of experimental autoimmune encephalitis in Lewis rats
AU - Della Valle, Brian William
AU - Brix, Gitte S.
AU - Brock, Birgitte
AU - Gejl, Michael
AU - Landau, Anne M.
AU - Moller, Arne
AU - Rungby, Jorgen
AU - Larsen, Agnete
PY - 2016/11/18
Y1 - 2016/11/18
N2 - Introduction: Recent findings indicate that metabolic disturbances are involved in multiple sclerosis (MS) pathology and influence the susceptibility to treatment, directing attention toward anti-diabetic drugs such as metformin and pioglitazone. Liraglutide, a drug of the glucagon-like peptide-1 (GLP-1) family, is also anti-diabetic and weight-reducing and is, moreover, directly neuroprotective and anti-inflammatory in a broad spectrum of experimental models of brain disease. In this study we investigate the potential for this FDA-approved drug, liraglutide, as a treatment for MS by utilizing the experimental model, experimental autoimmune encephalitis (EAE).Methods: EAE was induced in 30 female Lewis rats that subsequently received twice-daily liraglutide (200 μg/kg s.c.) or saline. Healthy controls were included (saline, n = 6, liraglutide, n = 7). Clinical score and weight were assessed daily by blinded observers. Animals were killed at peak disease severity (day 11) or if exceeding humane endpoint (clinical score ≥4). Protein levels of manganese superoxide dismutase (MnSOD), amyloid precursor protein (APP), and glial fibrillary acidic protein (GFAP) were determined.Results: Liraglutide treatment delayed disease onset (group clinical score significantly >0) by 2 days and markedly reduced disease severity (median clinical score 2 vs. 5; p = 0.0003). Fourteen of 15 (93%) of vehicle-treated rats reached the humane endpoint (clinical score ≥4) by day 11 compared to 5 of 15 (33%) of liraglutide-treated rats (p = 0.0004). Liraglutide substantially increased the mitochondrial antioxidant MnSOD (p < 0.01) and reduced the neurodegenerative marker APP (p = 0.036) in the brain. GFAP levels were not significantly changed with drug treatment (p = 0.09).Conclusion: We demonstrate, for the first time, that liraglutide treatment delays onset of EAE in Lewis rats and is associated with improved protective capacity against oxidative stress. These data suggest GLP-1 receptor agonists should be investigated further as a potential therapy for MS
AB - Introduction: Recent findings indicate that metabolic disturbances are involved in multiple sclerosis (MS) pathology and influence the susceptibility to treatment, directing attention toward anti-diabetic drugs such as metformin and pioglitazone. Liraglutide, a drug of the glucagon-like peptide-1 (GLP-1) family, is also anti-diabetic and weight-reducing and is, moreover, directly neuroprotective and anti-inflammatory in a broad spectrum of experimental models of brain disease. In this study we investigate the potential for this FDA-approved drug, liraglutide, as a treatment for MS by utilizing the experimental model, experimental autoimmune encephalitis (EAE).Methods: EAE was induced in 30 female Lewis rats that subsequently received twice-daily liraglutide (200 μg/kg s.c.) or saline. Healthy controls were included (saline, n = 6, liraglutide, n = 7). Clinical score and weight were assessed daily by blinded observers. Animals were killed at peak disease severity (day 11) or if exceeding humane endpoint (clinical score ≥4). Protein levels of manganese superoxide dismutase (MnSOD), amyloid precursor protein (APP), and glial fibrillary acidic protein (GFAP) were determined.Results: Liraglutide treatment delayed disease onset (group clinical score significantly >0) by 2 days and markedly reduced disease severity (median clinical score 2 vs. 5; p = 0.0003). Fourteen of 15 (93%) of vehicle-treated rats reached the humane endpoint (clinical score ≥4) by day 11 compared to 5 of 15 (33%) of liraglutide-treated rats (p = 0.0004). Liraglutide substantially increased the mitochondrial antioxidant MnSOD (p < 0.01) and reduced the neurodegenerative marker APP (p = 0.036) in the brain. GFAP levels were not significantly changed with drug treatment (p = 0.09).Conclusion: We demonstrate, for the first time, that liraglutide treatment delays onset of EAE in Lewis rats and is associated with improved protective capacity against oxidative stress. These data suggest GLP-1 receptor agonists should be investigated further as a potential therapy for MS
KW - GLP-1
KW - EAE
KW - multiplesclerosis
KW - liraglutide
KW - MS
KW - MnSOD
KW - APP
U2 - 10.3389/fphar.2016.00433
DO - 10.3389/fphar.2016.00433
M3 - Journal article
C2 - 27917122
VL - 7
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
SN - 1663-9812
M1 - 433
ER -
ID: 169941640