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 Detalle_Publicacion

Drug discovery for psychiatric disorders using high-content single-cell screening of signaling network responses ex vivo

Abstract: There is a paucity of efficacious new compounds to treat neuropsychiatric disorders. We present a novel approach to neuropsychiatric drug discovery based on high-content characterization of druggable signaling network responses at the single-cell level in patient-derived lymphocytes ex vivo. Primary T lymphocytes showed functional responses encompassing neuropsychiatric medications and central nervous system ligands at established (e.g., GSK-3?) and emerging (e.g., CrkL) drug targets. Clinical application of the platform to schizophrenia patients over the course of antipsychotic treatment revealed therapeutic targets within the phospholipase C?1-calcium signaling pathway. Compound library screening against the target phenotype identified subsets of L-type calcium channel blockers and corticosteroids as novel therapeutically relevant drug classes with corresponding activity in neuronal cells. The screening results were validated by predicting in vivo efficacy in an independent schizophrenia cohort. The approach has the potential to discern new drug targets and accelerate drug discovery and personalized medicine for neuropsychiatric conditions.

 Fuente: Sci Adv . 2019 May 8;5(5):eaau9093

Editorial: American Association for the Advancement of Science

 Año de publicación: 2019

Nº de páginas: 18

Tipo de publicación: Artículo de Revista

 DOI: 10.1126/sciadv.aau9093

ISSN: 2375-2548

Url de la publicación: https://www.doi.org/10.1126/sciadv.aau9093

Autores/as

LAGO, SANTIAGO G.

TOMASIK, JAKUB

REES, GEERTJE F. VAN

STEEB, HANNAH

COX, DAVID A.

RUSTOGI, NITIN

RAMSEY, JORDAN M.

BISHOP, JOSHUA A.

PETRYSHEN, TRACEY

HAGGARTY, STEPHEN J.

PAPIOL, SERGI

BEVEREN, NICO J. VAN

BAHN, SABINE