The GLP-1 receptor agonist, liraglutide, fails to slow disease progression in SOD1G93A and TDP-43Q331K transgenic mouse models of ALS

Abstract GLP-1 receptor agonists used for the treatment of diabetes, have shown some neuroprotective effects in cellular and animal models of Alzheimer’s disease (AD) and Parkinson’s disease (PD). There are currently few studies investigating GLP-1 receptor agonists in the treatment of ALS, where th...

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Autores principales:	Amy Keerie, Heledd Brown-Wright, Isaac Kirkland, Andrew Grierson, James J. P. Alix, Christian Holscher, Richard J. Mead
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8ad89c55f0164a14a6f498f5d3f6500b
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spelling	oai:doaj.org-article:8ad89c55f0164a14a6f498f5d3f6500b2021-12-02T15:09:23ZThe GLP-1 receptor agonist, liraglutide, fails to slow disease progression in SOD1G93A and TDP-43Q331K transgenic mouse models of ALS10.1038/s41598-021-96418-02045-2322https://doaj.org/article/8ad89c55f0164a14a6f498f5d3f6500b2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96418-0https://doaj.org/toc/2045-2322Abstract GLP-1 receptor agonists used for the treatment of diabetes, have shown some neuroprotective effects in cellular and animal models of Alzheimer’s disease (AD) and Parkinson’s disease (PD). There are currently few studies investigating GLP-1 receptor agonists in the treatment of ALS, where these neuroprotective effects may be beneficial. Here we investigate the effects of liraglutide, a GLP-1 receptor agonist, in two well characterised transgenic mouse models of ALS (SOD1G93A and TDP-43Q331K) to determine if liraglutide could be a potential treatment in ALS patients. Doses of liraglutide previously shown to have efficacy in AD and PD mouse models were used. Behavioural testing was carried out to ascertain the effect of liraglutide on disease progression. Immunohistochemical analysis of tissue was used to determine any neuroprotective effects on the CNS. We found that liraglutide dosed animals showed no significant differences in disease progression when compared to vehicle dosed animals in either the SOD1G93A or TDP-43Q331K mouse models of ALS. We also observed no changes in motor neuron counts or glial activation in lumbar spinal cords of liraglutide treated mice compared to vehicle dosed mice. Overall, we found no evidence to support clinical evaluation of liraglutide as a potential candidate for the treatment of ALS.Amy KeerieHeledd Brown-WrightIsaac KirklandAndrew GriersonJames J. P. AlixChristian HolscherRichard J. MeadNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Amy Keerie Heledd Brown-Wright Isaac Kirkland Andrew Grierson James J. P. Alix Christian Holscher Richard J. Mead The GLP-1 receptor agonist, liraglutide, fails to slow disease progression in SOD1G93A and TDP-43Q331K transgenic mouse models of ALS
description	Abstract GLP-1 receptor agonists used for the treatment of diabetes, have shown some neuroprotective effects in cellular and animal models of Alzheimer’s disease (AD) and Parkinson’s disease (PD). There are currently few studies investigating GLP-1 receptor agonists in the treatment of ALS, where these neuroprotective effects may be beneficial. Here we investigate the effects of liraglutide, a GLP-1 receptor agonist, in two well characterised transgenic mouse models of ALS (SOD1G93A and TDP-43Q331K) to determine if liraglutide could be a potential treatment in ALS patients. Doses of liraglutide previously shown to have efficacy in AD and PD mouse models were used. Behavioural testing was carried out to ascertain the effect of liraglutide on disease progression. Immunohistochemical analysis of tissue was used to determine any neuroprotective effects on the CNS. We found that liraglutide dosed animals showed no significant differences in disease progression when compared to vehicle dosed animals in either the SOD1G93A or TDP-43Q331K mouse models of ALS. We also observed no changes in motor neuron counts or glial activation in lumbar spinal cords of liraglutide treated mice compared to vehicle dosed mice. Overall, we found no evidence to support clinical evaluation of liraglutide as a potential candidate for the treatment of ALS.
format	article
author	Amy Keerie Heledd Brown-Wright Isaac Kirkland Andrew Grierson James J. P. Alix Christian Holscher Richard J. Mead
author_facet	Amy Keerie Heledd Brown-Wright Isaac Kirkland Andrew Grierson James J. P. Alix Christian Holscher Richard J. Mead
author_sort	Amy Keerie
title	The GLP-1 receptor agonist, liraglutide, fails to slow disease progression in SOD1G93A and TDP-43Q331K transgenic mouse models of ALS
title_short	The GLP-1 receptor agonist, liraglutide, fails to slow disease progression in SOD1G93A and TDP-43Q331K transgenic mouse models of ALS
title_full	The GLP-1 receptor agonist, liraglutide, fails to slow disease progression in SOD1G93A and TDP-43Q331K transgenic mouse models of ALS
title_fullStr	The GLP-1 receptor agonist, liraglutide, fails to slow disease progression in SOD1G93A and TDP-43Q331K transgenic mouse models of ALS
title_full_unstemmed	The GLP-1 receptor agonist, liraglutide, fails to slow disease progression in SOD1G93A and TDP-43Q331K transgenic mouse models of ALS
title_sort	glp-1 receptor agonist, liraglutide, fails to slow disease progression in sod1g93a and tdp-43q331k transgenic mouse models of als
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8ad89c55f0164a14a6f498f5d3f6500b
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The GLP-1 receptor agonist, liraglutide, fails to slow disease progression in SOD1G93A and TDP-43Q331K transgenic mouse models of ALS

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