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Publication : The GLP-1 receptor agonist, liraglutide, fails to slow disease progression in SOD1(G93A) and TDP-43(Q331K) transgenic mouse models of ALS.

First Author  Keerie A Year  2021
Journal  Sci Rep Volume  11
Issue  1 Pages  17027
PubMed ID  34426623 Mgi Jnum  J:359850
Mgi Id  MGI:6754901 Doi  10.1038/s41598-021-96418-0
Citation  Keerie A, et al. (2021) The GLP-1 receptor agonist, liraglutide, fails to slow disease progression in SOD1(G93A) and TDP-43(Q331K) transgenic mouse models of ALS. Sci Rep 11(1):17027
abstractText  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 (SOD1(G93A) and TDP-43(Q331K)) 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 SOD1(G93A) or TDP-43(Q331K) 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.
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