Alzheimer's disease (AD) is the most common neurodegenerative disorder. Epigenetic modifications may play a role in the onset and progression of these diseases. REST is a key transcription factor that modulates the expression of key neuronal genes.. It binds to its DNA targets and assembles a transcriptional repressor complex containing HDAC1/2, CoREST and LSD1 among others. Inappropriate REST activity in neuronal cells is expected to repress the expression of key neuronal genes like BDNF. Rest mRNA expression is up-regulated in AD and inversely correlated with Uchl1 expression a proteasome biomarker related with neurodegenerative diseases ad AD, PD, FTD and others. Our strategy is to redress transcriptional changes or imbalances in AD by inhibition of components of the REST repressor complex. We chose LSD1. We have developed ORY-2001, a dual LSD1/MAO-B inhibitor, with excellent pharmacological and ADME-PK properties. We have shown that 2 - 4 months of oral treatment with ORY-2001 stops the cognitive impairment and restores the memory deficit of SAMP-8 AD model mice. In the current project, we propose to develop an adequate human formulation for oral once-daily administration, to perform the regulatory toxicology IND-enabling studies and to prepare the whole regulatory package to obtain the IND/CTA permissions to start a Phase I clinical trial in humans and to to develop the clinical plan for ORY-2001.