Human genome-guided identification of memory-modulating drugs

Area of Science:

• Neuroscience
• Genetics
• Pharmacology

Background:

• Advances in understanding the genetic basis of complex human traits, including neuropsychiatric disorders, have increased.
• The utility of this genetic knowledge for drug discovery remains a key question for the human genome project.

Purpose of the Study:

• To identify compounds that modulate memory using human genetic information.
• To provide proof of concept for genome-guided drug identification for memory modulation.

Main Methods:

• A multinational collaborative study assessed aversive memory in healthy individuals.
• Gene-set analysis identified potential drug target genes within genomewide-corrected gene sets.
• A double-blind, placebo-controlled study tested pharmacological interventions.

Main Results:

• Twenty potential drug target genes were identified in the neuroactive ligand-receptor interaction and long-term depression gene sets.
• Pharmacological intervention targeting the neuroactive ligand-receptor interaction gene set significantly reduced aversive memory.

Conclusions:

• Human genome information, coupled with data mining, can serve as a foundation for identifying memory-modulating compounds.
• This approach offers a novel strategy for drug discovery in areas like posttraumatic stress disorder.