Preclinical research in Rett syndrome: Setting the foundation for translational success
David M. Katz,Joanne Berger-Sweeney,James H. Eubanks,Monica J. Justice,Jeffrey L. Neul,Lucas Pozzo-Miller,Mary E. Blue,Diana Christian,Jacqueline N. Crawley,Maurizio Giustetto,Jacky Guy,C. James Howell,Miriam Kron,Sacha B. Nelson,Rodney C. Samaco,Laura Schaevitz,Coryse St Hillaire-Clarke,Juan L. Young,Huda Y. Zoghbi,Huda Y. Zoghbi,Laura A. Mamounas +20 more
TLDR
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 are summarized.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.read more
Citations
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Excitatory/Inhibitory Balance and Circuit Homeostasis in Autism Spectrum Disorders.
Sacha B. Nelson,Vera Valakh +1 more
TL;DR: The contrasting evidence for primary defects in inhibition or excitation in ASDs is explored and the findings are integrated in terms of the brain's ability to maintain functional homeostasis.
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Threats to validity in the design and conduct of preclinical efficacy studies: a systematic review of guidelines for in vivo animal experiments
Valerie C. Henderson,Jonathan Kimmelman,Dean Fergusson,Dean Fergusson,Jeremy M. Grimshaw,Jeremy M. Grimshaw,Daniel G. Hackam +6 more
TL;DR: A systematic review of preclinical research guidelines and organized recommendations according to the type of validity threat (internal, construct, or external) or programmatic research activity they primarily address provided a starting point for developing preclinical guidelines in other disease domains.
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The GABAA Receptor as a Therapeutic Target for Neurodevelopmental Disorders
Sien Braat,R. Frank Kooy +1 more
TL;DR: It is argued that the GABAergic system is disturbed in many neurodevelopmental disorders, including fragile X syndrome, Rett Syndrome, and Dravet syndrome, and is a key candidate target for therapeutic intervention.
Journal ArticleDOI
GABAergic signaling as therapeutic target for autism spectrum disorders
Giada Cellot,Enrico Cherubini +1 more
TL;DR: How changes of GABAA-mediated neurotransmission affect several forms of ASDs including the Fragile X, the Angelman, and Rett syndromes are discussed, and reverting the polarity of GABA responses from the depolarizing to the hyperpolarizing direction with the diuretic bumetanide, a selective blocker of NKCC1 is discussed.
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MECP2 disorders: from the clinic to mice and back
TL;DR: The clinical profiles of MECP2 disorders, the knowledge acquired from mouse models of the syndromes, and how that knowledge is informing current and future clinical studies are discussed.
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