{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:01:41Z","timestamp":1790006501044,"version":"4.0.1"},"reference-count":56,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,8,19]],"date-time":"2020-08-19T00:00:00Z","timestamp":1597795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    There is currently no therapy impacting the course of amyotrophic lateral sclerosis (ALS). The only approved treatments are riluzole and edaravone, but their efficacy is modest and short\u2010lasting, highlighting the need for innovative therapies. We previously demonstrated the ability of PXT864, a combination of low doses of acamprosate and baclofen, to synergistically restore cellular and behavioral activity in Alzheimer's and Parkinson's disease models. The overlapping genetic, molecular, and cellular characteristics of these neurodegenerative diseases supported investigating the effectiveness of PXT864 in ALS. As neuromuscular junction (NMJ) alterations is a key feature of ALS, the effects of PXT864 in primary neuron\u2010muscle cocultures injured by glutamate were studied. PXT864 significantly and synergistically preserved NMJ and motoneuron integrity following glutamate excitotoxicity. PXT864 added to riluzole significantly improved such protection. PXT864 activity was then assessed in primary cultures of motoneurons derived from SOD1\n                    <jats:sup>G93A<\/jats:sup>\n                    rat embryos. These motoneurons presented severe maturation defects that were significantly improved by PXT864. In this model, glutamate application induced an accumulation of TDP\u201043 protein in the cytoplasm, a hallmark that was completely prevented by PXT864. The anti\u2010TDP\u201043 aggregation effect was also confirmed in a cell line expressing TDP\u201043 fused to GFP. These results demonstrate the value of PXT864 as a promising therapeutic strategy for the treatment of ALS.\n                  <\/jats:p>","DOI":"10.1002\/jnr.24714","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T05:51:27Z","timestamp":1598593887000},"page":"2435-2450","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Combination of acamprosate and baclofen (PXT864) as a potential new therapy for amyotrophic lateral sclerosis"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6038-2547","authenticated-orcid":false,"given":"Lydie","family":"Boussicault","sequence":"first","affiliation":[{"name":"PHARNEXT Paris 75009 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Laffaire","sequence":"additional","affiliation":[{"name":"PHARNEXT Paris 75009 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