title: Rett Syndrome: Crossing the Threshold to Clinical Translation.
abstract: Lying at the intersection between neurobiology and epigenetics, Rett syndrome (RTT) has garnered intense interest in recent years, not only from a broad range of academic scientists, but also from the pharmaceutical and biotechnology industries. In addition to the critical need for treatments for this devastating disorder, optimism for developing RTT treatments derives from a unique convergence of factors, including a known monogenic cause, reversibility of symptoms in preclinical models, a strong clinical research infrastructure highlighted by an NIH-funded natural history study and well-established clinics with significant patient populations. Here, we review recent advances in understanding the biology of RTT, particularly promising preclinical findings, lessons from past clinical trials, and critical elements of trial design for rare disorders.
authors.affiliation: Departments of Neurosciences and Psychiatry, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA. Electronic address: david.katz@case.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Katz
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: Adrian
authors.initials: A
authors.lastname: Bird
authors.affiliation: Rett Syndrome Research Trust, 67 Under Cliff Road, Trumbull, CT 06611, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Coenraads
authors.affiliation: Gene Therapy Center and Department of Ophthalmology, University of North Carolina, Chapel Hill, NC USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Gray
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Debashish U
authors.initials: DU
authors.lastname: Menon
authors.affiliation: Department of Cell Biology and Physiology, Neuroscience Center, and Carolina Institute for Developmental Disabilities, UNC School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Philpot
authors.affiliation: Children's Healthcare of Atlanta, Emory University, 1605 Chantilly Drive NE, Atlanta, GA 30324, USA.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Tarquinio
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic / Q000379:methods; D044127:Epigenesis, Genetic / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics; D015518:Rett Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D057170:Translational Research, Biomedical / Q000379:methods / Q000639:trends*
keywords: MECP2; clinical trials; epigenetics; gene therapy; neurodevelopmental disorders; preclinical models
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