A Transcriptome‐Based Drug Discovery Paradigm for Neurodevelopmental Disorders

Advances in genetic discoveries have created substantial opportunities for precision medicine in neurodevelopmental disorders. Many of the genes implicated in these diseases encode proteins that regulate gene expression, such as chromatin‐associated proteins, transcription factors, and RNA‐binding p...

Full description

Saved in:
Bibliographic Details
Published in:Annals of neurology 2021-02, Vol.89 (2), p.199-211
Main Authors: Dhindsa, Ryan S., Zoghbi, Anthony W., Krizay, Daniel K., Vasavda, Chirag, Goldstein, David B.
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Anticonvulsants - pharmacology
Antidepressive Agents - pharmacology
Antipsychotic Agents - pharmacology
Carbamazepine - pharmacology
Chromatin
Computer Simulation
Disorders
Drug Discovery
Epirizole - pharmacology
Gene expression
Gene Expression Profiling
Gene Expression Regulation - genetics
Genes
Humans
Induced Pluripotent Stem Cells
MCF-7 Cells
Mice
Mutation
Naloxone - pharmacology
Narcotic Antagonists - pharmacology
Neural Stem Cells - drug effects
Neural Stem Cells - metabolism
Neurodevelopmental disorders
Neurodevelopmental Disorders - drug therapy
Neurodevelopmental Disorders - genetics
Neurons - drug effects
Neurons - metabolism
PC-3 Cells
Perphenazine - pharmacology
Precision medicine
Primary Cell Culture
Proteins
Ribonucleic acid
Risperidone - pharmacology
RNA
RNA-Seq
Single-Cell Analysis
Transcription factors
Transcriptome - drug effects
Transcriptomes
Trazodone - pharmacology
Trimipramine - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Advances in genetic discoveries have created substantial opportunities for precision medicine in neurodevelopmental disorders. Many of the genes implicated in these diseases encode proteins that regulate gene expression, such as chromatin‐associated proteins, transcription factors, and RNA‐binding proteins. The identification of targeted therapeutics for individuals carrying mutations in these genes remains a challenge, as the encoded proteins can theoretically regulate thousands of downstream targets in a considerable number of cell types. Here, we propose the application of a drug discovery approach originally developed for cancer called “transcriptome reversal” for these neurodevelopmental disorders. This approach attempts to identify compounds that reverse gene‐expression signatures associated with disease states. ANN NEUROL 2021;89:199–211
ISSN:0364-5134
1531-8249
DOI:10.1002/ana.25950