Glucagon-Like Peptide-1 Analog, Liraglutide, Delays Onset of Experimental Autoimmune Encephalitis in Lewis Rats
Open accessAbstract
Introduction: Recent findings indicate that metabolic disturbances are involved in multiple sclerosis (MS) pathology and influence the susceptibility to treatment, directing attention towards 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 two 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. Keywords: GLP-1, EAE, Multiple Sclerosis, liraglutide, MS, MnSOD, APP
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The neuroprotective effect of GLP-1 is effective in AD and PD, and also in other NDD such as HD, ALS, and MS.
“The neuroprotective effect of GLP-1 is not only effective in AD and PD, but also in other NDD such as HD (Duarte et al. 2018), ALS (Li et al. 2012), and MS (DellaValle et al. 2016).”
From Therapeutic effect of GLP-1 engineered strain on mice model of Alzheimer’s disease and Parkinson’s disease (2020) · cites this paper as DellaValle et al. 2016
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- Authors
- DellaValle, B., Brix, G. S., Brock, B., Gejl, M., Landau, A. M., Møller, A., Rungby, J., & Larsen, A.
- Affiliations
- University of Copenhagen (DK)
- Aarhus University (DK)
- Corresponding author
- Larsen, Agnete
- ORCID
- Venue
- Frontiers in Pharmacology
- Publisher
- Frontiers Media SA
- Published
- 2016-11-18
- Volume
- 7
- Pages
- 433-433
- ISSN
- 1663-9812 (ISSN-L)
- PMC
- PMC5114298
- OpenAlex
- W2554239825
- Cited by
- 39
- References
- 26
- Citations by year
- 2026: 9 · 2025: 5 · 2024: 4 · 2023: 1 · 2022: 6 · 2021: 3 · 2020: 1 · 2019: 5 · 2018: 3 · 2017: 2
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Pharmacology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Health Sciences › Medicine › Neurology › Autoimmune Neurological Disorders and Treatments
- Keywords
- liraglutide, GLP-1 receptor agonists, experimental autoimmune encephalitis, multiple sclerosis, disease onset delay, oxidative stress, manganese superoxide dismutase, amyloid precursor protein, neurodegeneration, neuroprotection, Lewis rats, glial fibrillary acidic protein, anti-inflammatory activity
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