Pharnext, a pharmaceutical company specialized in neurological diseases has just published an article in a famous review (Nature Scientific Reports) demonstrating, in the case of a pre-clinical study, the benefits of the PXT-864 for the treatment of Alzheimer’s disease.

According to the fact that neurological diseases are often complex and multifactorial, Pharnext SAS opts for an original therapeutic strategy “the Pleotherapy” targeting in the same treatment several aspects of the pathology. It consists in providing a combination of molecules with additive or synergistic actions already having a market authorization to treat other diseases then rendering unnecessary phase I clinical studies

Alzheimer’s disease is a neurodegenerative disease linked to age, resulting in cortical atrophy that first impairs the temporal lobe region of the brain involved in memory and then spreads to the frontal associative and temporo-parietal cortex. It causes severe cognitive disorders including dysfunction of memory and behavior. Neuronal degeneration continues until the loss of autonomic functions and death. The brain of patients is characterized by an accumulation of extracellular β-amyloid peptide called “amyloid plate”. This disease affects approximately 25 million people in the world and there is currently no effective treatment.

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Several cellular mechanisms have been implicated in neurodegenerative events observed in this disease. Among them, an imbalance between excitatory (mainly glutamate) and inhibitory neurotransmitters (gamma-aminobutyric acid or GABA, glycine) would alter cognitive functions and induce the release of pro-apoptotic molecules promoting neuronal death.

With the administration of PXT-864 targeting this signaling pathway, Pharnext hopes to restore the balance of excitatory / inhibitory signals. Thus, the PXT-864 is derived from the combination of Baclofen, agonist of the metabotropic GABA B receptor and potentially of the glycine receptor, already used as a muscle relaxant to reduce spastic contractures in multiple sclerosis and Acamprosate calcium, inhibitor of the receptor N-methyl-D-aspartate glutamate (NMDA) prescribed to treat alcohol disorders.

Studies performed in vitro and in vivo show a synergistic action of the two compounds and an improvement of several cellular and behavioral parameters. The PXT-864 is able to protect neurons from the β-amyloid induced toxicity due to its multifactorial action, including the regulation of glutamate levels, oxidative stress and synapses protection. Moreover, in vivo studies in rodent models have shown a significant reduction of cognitive deficits and inflammatory response.

These very encouraging results are continuing in a clinical Phase IIa study that opens new therapeutic perspectives.

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