Oryzon Genomics, S.A. announced the start of a precision medicine collaboration in schizophrenia (SCZ) with researchers from Columbia University in New York, Dr. Joseph Gogos, Dr. Sander Markx and Dr. Jeffrey Lieberman. SETD1A is a histone methyltransferase that is a key SCZ susceptibility gene. This project has two parts: the first is to further characterize the therapeutic actionability of the SETD1A regulator protein encoded by this gene with LSD1 inhibitors at the molecular level in preclinical Setd1a models. The second is to perform exhaustive functional psychometric characterization of individuals carrying mutations in the SETD1A gene to build a foundation for a subsequent precision psychiatry clinical trial with vafidemstat for SETD1A-associated psychiatric disorders. Recent work published by Dr. Gogos’ laboratory at Columbia University has shown that heterozygous loss-of-function (LOF) mutation of the Setd1a gene in mice results in alterations in axonal branching and cortical synaptic dynamics, accompanied by specific deficits in working memory that recapitulate human SCZ-related cognitive and behavioral deficits. Critically, administration of an Oryzon’s LSD1 inhibitor produced a full rescue of both the behavioral and neuronal disease phenotypes. This work specifically demonstrated that these treatment effects occur in adult animals suggesting that deficiency of Setd1a function during early developmental stages does not irreversibly compromise the function of disease-related neural circuits. This finding opens the door for investigation of intervention with vafidemstat during a therapeutic window in adolescent and adult subjects. Patients harboring inherited mutations in SETD1A have been identified in the Amish founder population in Pennsylvania. Dr. Markx, who is Professor of Psychiatry at Columbia University and the leader of the Columbia Precision Psychiatry group, will conduct a pilot study to characterize clinical profile of these individuals to determine their different degrees of cognitive impairment. This study will inform the potential actionability of the SETD1A regulator protein by inhibition of LSD1 and the best endpoints for a future clinical study with vafidemstat.