Preclinical research in Rett syndrome: Setting the foundation for translational success

David M. Katz, Joanne E. Berger-Sweeney, James H. Eubanks, Monica J. Justice, Jeffrey L. Neul, Lucas Pozzo-Miller, Mary E. Blue, Diana Christian, Jacqueline Crawley, Maurizio Giustetto, Jacky Guy, C. James Howell, Miriam Kron, Sacha B. Nelson, Rodney C. Samaco, Laura R. Schaevitz, Coryse St Hillaire-Clarke, Juan L. Young, Huda Y. Zoghbi, Laura A. Mamounas

Research output: Contribution to journalArticle

117 Scopus citations

Abstract

In September of 2011, the National Institute of Neurological Disorders and Stroke (NINDS), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the International Rett Syndrome Foundation (IRSF) and the Rett Syndrome Research Trust (RSRT) convened a workshop involving a broad cross-section of basic scientists, clinicians and representatives from the National Institutes of Health (NIH), the US Food and Drug Administration (FDA), the pharmaceutical industry and private foundations to assess the state of the art in animal studies of Rett syndrome (RTT). The aim of the workshop was to identify crucial knowledge gaps and to suggest scientific priorities and best practices for the use of animal models in preclinical evaluation of potential new RTT therapeutics. This review summarizes outcomes from the workshop and extensive follow-up discussions among participants, and includes: (1) a comprehensive summary of the physiological and behavioral phenotypes of RTT mouse models to date, and areas in which further phenotypic analyses are required to enhance the utility of these models for translational studies; (2) discussion of the impact of genetic differences among mouse models, and methodological differences among laboratories, on the expression and analysis, respectively, of phenotypic traits; and (3) definitions of the standards that the community of RTT researchers can implement for rigorous preclinical study design and transparent reporting to ensure that decisions to initiate costly clinical trials are grounded in reliable preclinical data.

Original languageEnglish (US)
Pages (from-to)733-745
Number of pages13
JournalDMM Disease Models and Mechanisms
Volume5
Issue number6
DOIs
StatePublished - Nov 2012

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine (miscellaneous)
  • Immunology and Microbiology (miscellaneous)
  • Neuroscience (miscellaneous)

Cite this

Katz, D. M., Berger-Sweeney, J. E., Eubanks, J. H., Justice, M. J., Neul, J. L., Pozzo-Miller, L., Blue, M. E., Christian, D., Crawley, J., Giustetto, M., Guy, J., Howell, C. J., Kron, M., Nelson, S. B., Samaco, R. C., Schaevitz, L. R., Hillaire-Clarke, C. S., Young, J. L., Zoghbi, H. Y., & Mamounas, L. A. (2012). Preclinical research in Rett syndrome: Setting the foundation for translational success. DMM Disease Models and Mechanisms, 5(6), 733-745. https://doi.org/10.1242/dmm.011007