• Alzheimer's disease (AD) is particularly devastating since there is no cure, no way to prevent it and no proven way to slow its progression.

• Management of AD represents a huge unmet need; thus, discovery and development of more effective therapies are critical for worldwide public health and health-care systems.

• Novel strategy for symptomatic & disease-modifying treatment of Alzheimer's disease hitting two targets, epigenetic (HDAC) and non-epigenetic (PDES). Proof of Concept using reference compounds (vorinostat and tadalafil).

  • In vitro, using primary neuronal cultures: synergistic effect on epigenetic mark (histone acetylation).

  • Ex vivo, using hippocampal slices from AD mice (APP/PS1): synergistic effect in long term potentiation (LTP).

  • In vivo,  using AD mice (Tg2576): behavior studies and AD pathological marks.

• Novel proprietary compounds, first‐in class dual inhibitors (HDAC and PDE5) show safety and efficacy in reversing AD phenotype using transgenic mice (APP/PS1, Tg2576).

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• There is an unmet need for effective therapeutic strategies in Huntington's disease (HD) and drug abuse. 

• GluN3A is a novel target that regulates synapse plasticity and neuronal connectivity.

  • Its expression is reactivated in CNS pathologies including HD, cocaine and alcohol abuse.

  • Proof of Concept: Knock-Out mice in HD and shRNA in drug abuse.

  • Safety:  lacking in healthy adult brain.