Molecular Systems Biology of Neurodevelopmental Disorders, Rett Syndrome as an Archetype.
Rett
autism
biomarker
clinical trials
genealogical proteomics
precision medicine
Journal
Frontiers in integrative neuroscience
ISSN: 1662-5145
Titre abrégé: Front Integr Neurosci
Pays: Switzerland
ID NLM: 101477950
Informations de publication
Date de publication:
2019
2019
Historique:
received:
26
04
2019
accepted:
02
07
2019
entrez:
6
8
2019
pubmed:
6
8
2019
medline:
6
8
2019
Statut:
epublish
Résumé
Neurodevelopmental disorders represent a challenging biological and medical problem due to their genetic and phenotypic complexity. In many cases, we lack the comprehensive understanding of disease mechanisms necessary for targeted therapeutic development. One key component that could improve both mechanistic understanding and clinical trial design is reliable molecular biomarkers. Presently, no objective biological markers exist to evaluate most neurodevelopmental disorders. Here, we discuss how systems biology and "omic" approaches can address the mechanistic and biomarker limitations in these afflictions. We present heuristic principles for testing the potential of systems biology to identify mechanisms and biomarkers of disease in the example of Rett syndrome, a neurodevelopmental disorder caused by a well-defined monogenic defect in methyl-CpG-binding protein 2 (MECP2). We propose that such an approach can not only aid in monitoring clinical disease severity but also provide a measure of target engagement in clinical trials. By deepening our understanding of the "big picture" of systems biology, this approach could even help generate hypotheses for drug development programs, hopefully resulting in new treatments for these devastating conditions.
Identifiants
pubmed: 31379529
doi: 10.3389/fnint.2019.00030
pmc: PMC6650571
doi:
Types de publication
Journal Article
Langues
eng
Pagination
30Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM103449
Pays : United States
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