Rett Syndrome: Crossing the Threshold to Clinical Translation

• Type of Material: Article
• Authors: David M. Katz, Case Western Reserve University; Adrian Bird, University of Edinburgh; Monica Coenraads, Rett Syndrome Research Trust; Steven J. Gray, University of North Carolina; Debashish U. Menon, University of North Carolina; Benjamin D. Philpot, University of North Carolina; Daniel Tarquinio, Emory University
• Language: English
• Date: 2016-02-01
• Publisher: Elsevier (Cell Press)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 Published by Elsevier Ltd.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.tins.2015.12.008
• Title of Journal or Parent Work: Trends in Neurosciences
• ISSN: 0166-2236
• Volume: 39
• Issue: 2
• Start Page: 100
• End Page: 113
• Grant/Funding Information: This work was supported by grants awarded to D.M.K. from NINDS (RO1NS057398) and the Rett Syndrome Research Trust (RSRT); to A.B. from The Wellcome Trust (grants 091580 and 092076) and RSRT; to B.D.P. from the Simons Foundation (SFARI Award 274426), NINDS (R01NS085093), NIMH (R01MH093372), and RSRT; to S.J.G. from Rettsyndrome.org, RSRT and Research to Prevent Blindness through the UNC Department of Ophthalmology; to D.U.M. from NICHD (RO1HD036655; T. Magnuson, PI).
• Keywords: DNA-METHYLATION; NATURAL-HISTORY; Neurosciences & Neurology; PYRAMIDAL NEURONS; MOUSE MODEL; Science & Technology; Life Sciences & Biomedicine; RARE DISEASES; DUCHENNE MUSCULAR-DYSTROPHY; MECP2 KNOCKOUT MICE; CPG BINDING DOMAIN; SEVERE MENTAL-RETARDATION; Neurosciences; TRANSCRIPTIONAL REPRESSOR
• Research Categories: Health Sciences, General; Biology, Genetics; Biology, Neuroscience

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.