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EHDN 2022 | Pridopidine rescues BDNF transport in a Huntington’s disease brain-on-a-chip model

Frederic Saudou, PhD, Université Grenoble Alpes, Grenoble, France, shares the findings of a study investigating the impact of pridopidine on axonal transport in a Huntington disease (HD) brain-on-a-chip model. Huntingtin (HTT) is involved in the axonal transport of vesicles containing BDNF, notably in the corticostriatal circuitry, and in HD, mutations in HTT lead to a reduced transport efficiency. Less BDNF is delivered to the striatum which is thought to contribute to striatal and cortical neuronal death. Pridopidine is a selective sigma-1 receptor (S1R) agonist under investigation for the treatment of HD. Using cultured primary neurons from an HD mouse model, the investigators developed a “disease-on-a-chip” platform mimicking the corticostriatal network. Treatment with pridopidine was shown to rescue the reduced BDNF trafficking, as well as increase the capacity of HD neurons to release glutamate and restore synaptic homeostasis. Other small molecules that could act on this system are also under investigation. This interview took place during the European Huntington’s Disease Network 2022 Plenary Meeting.

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