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Author Notes:

Correspondence: Daniel Tarquinio: daniel@rareneuro.com

Author Contributions: DT and VF participated in study conceptualization, conduct of review, data collection, manuscript preparation, and approved the final manuscript as submitted.

MW and AC participated in manuscript preparation, and approved the final manuscript as submitted.

Acknowledgments: We thank the Rett Syndrome Research Trust for their generous support, and are deeply indebted to the families who have contributed their time to an improved understanding of neurodevelopmental disorders.

Conflict of Interest Statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Subjects:

Research Funding:

VF is supported by grants from the Rett Syndrome Research Trust and NIH 1R56MH111459. DT is supported by grants from the Rett Syndrome Research Trust.

MW is supported by the NIH Training Grant T32 GM08605.

AC is supported by an Institutional Development Award (IDeA) from the National Institute of General Medicine of the National Institutes of Health under grant number P20GM103449.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Behavioral Sciences
  • Neurosciences
  • Neurosciences & Neurology
  • Rett
  • autism
  • biomarker
  • clinical trials
  • genealogical proteomics
  • precision medicine
  • X-CHROMOSOME INACTIVATION
  • MOUSE MODEL
  • MECP2 EXPRESSION
  • GENE-EXPRESSION
  • MESSENGER-RNA
  • MUTANT MICE
  • NEUROPSYCHIATRIC SYMPTOMS
  • PROTEIN ABUNDANCE
  • MUTATION TYPE
  • BRAIN

Molecular Systems Biology of Neurodevelopmental Disorders, Rett Syndrome as an Archetype

Tools:

Journal Title:

Frontiers in Integrative Neuroscience

Volume:

Volume 13

Publisher:

, Pages 30-30

Type of Work:

Article | Final Publisher PDF

Abstract:

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.

Copyright information:

© 2019 Faundez, Wynne, Crocker and Tarquinio.

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