Clioquinol as a new therapy in epilepsy: From preclinical evidence to a proof-of-concept clinical study.

ABSTRACT:

Objective

Drug-resistant epilepsy (DRE) affects >25 million people worldwide and is often associated with neuroinflammation. Increasing evidence links deficiency or malfunctioning of the enzyme phosphoglycerate dehydrogenase (PHGDH), which converts 3-phosphoglycerate to generate serine and the neurotransmitter glycine, with (drug-resistant) epilepsy. Moreover, PHGDH, which is primarily expressed in astrocytes within the brain, has been identified as a critical enzyme in driving macrophage polarization toward an anti-inflammatory state. Hence, PHGDH activators may be beneficial for treating DRE by exhibiting both antiseizure and anti-inflammatory activity. The objective of this study was to identify such PHGDH activators.

Methods

We screened a drug repurposing library for PHG

SUBMITTER: Thevissen K 

PROVIDER: S-EPMC12605802 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature