Combination of acamprosate and baclofen (PXT864) for ALS

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PXT864 is an example of a repurposed drug combination. It uses baclofen and acamprosate, taken twice a day. Baclophen is a derivative of γ-aminobutyric acid, aka GABA, and acts as a GABA-B receptor agonist. It is used as a muscle relaxant to treat spasticity, for example in cerebral palsy and multiple sclerosis. Acamprosate is a drug of unclear mechanism of action, which is used to treat alcohol dependence.

While no double blind phase I/II/III clinical trial has tested PXT864, two small studies tested it for Alzheimer disease in 2013 to 2015. There was also a publication in 2015 in Nature's Scientific reports about effects of PXT864 on a rat model of Parkinson disease (6-OHDA). They used stereotaxic injection rat model to assess the efficacy of the combination in vivo in 6-OHDA rats. This model offers the benefit that each animal serves as its own control.

In a new publication PXT864 activity was assessed in primary cultures of motoneurons derived from SOD1G93A rat embryos. These motoneurons presented severe maturation defects that were significantly improved by PXT864. In this model of ALS, glutamate application induced an accumulation of TDP-43 protein in the cytoplasm, a hallmark that was completely prevented by PXT864. The anti-TDP-43 aggregation effect was also confirmed in a cell line expressing TDP-43 fused to GFP. These results demonstrate the value of PXT864 as a promising therapeutic strategy for the treatment of ALS.

Testing in-vitro is cheap with respect to test with animal models, and it is well known that no animal model of neurodegenerescent diseases reflects what is happening in humans.

Typical of biotech players, Pharnext, which began in 2007, has had its struggles. It is deeply unprofitable but the driving force behind Pharnext’s strategy is its founder, Daniel Cohen, who led the team that mapped the human genome in the 1990s, and now functions as his company’s chief scientist.

Nevertheless baclofen and acamprosate are two common drugs, so this might interest many ALS patients. However both drugs have strong and indesirable side effects.


This book retraces the main achievements of ALS research over the last 30 years, presents the drugs under clinical trial, as well as ongoing research on future treatments likely to be able stop the disease in a few years and to provide a complete cure in a decade or two.

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