Dream Complex Inhibitors for Treating Medical Conditions Induced by Circadian Rhythm Disruption

Keywords

DREAM inhibitors, harmine, circadian rhythm disruption, sleep deprivation, restoring cellular and organismal homeostasis

Invention Novelty

PER1-targeting siRNA or Harmine-like inhibitors restore cellular and metabolic function in circadian rhythm disruption models without modifying sleep patterns.

Value Proposition

-Sleep cycle independent effect: DREAM inhibition shifts cells toward a sleep-phase, repair/maintenance state supporting a downstream-of-clock mechanism and enabling timed dosing

-Target engagement: In C. elegans, co-RNAi of DREAM subunits or harmine rescues paralysis in proteotoxic-stress models; in mouse cortex, sleep deprivation keeps DREAM high and disrupts the same pathways; human retinal cells replicate pathway rescue with harmine, demonstrating cross-species conservation

-MoA: Lowering DREAM decreases chromatin-compaction markers, rebalances OXPHOS/mitochondria, detoxification, tunes ribosome/transcription programs, and increases DNA-repair programs
Functional evidence suggests that the restorative benefits of sleep can be mimicked by DREAM inhibitors without changing sleep patterns.

Commercial Opportunity

The technology is available for co-development and in-licensing partnerships.

Development Status

Proof-of-concept established for DREAM modulation restoring cellular function under circadian disruption.

Patent Situation

A European patent was filed in December 2023 (EP23218648) followed by a PCT application (WO2025133144) in 2024.

Further Reading

Original publication – Santos Valentim et al., 2025. biorXiv.