MIT Libraries homeMIT Libraries logoDSpace@MIT

MIT
View Item 
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Drug development for neurodevelopmental disorders: lessons learned from fragile X syndrome

Author(s)
Berry-Kravis, Elizabeth M.; Lindemann, Lothar; Jønch, Aia E.; Apostol, George; Bear, Mark; Carpenter, Randall L; Crawley, Jacqueline N.; Curie, Aurore; Des Portes, Vincent; Hossain, Farah; Gasparini, Fabrizio; Gomez-Mancilla, Baltazar; Hessl, David; Loth, Eva; Scharf, Sebastian H.; Wang, Paul P.; Von Raison, Florian; Hagerman, Randi; Spooren, Will; Jacquemont, Sébastien; ... Show more Show less
Thumbnail
DownloadAccepted version (703.7Kb)
Terms of use
Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/
Metadata
Show full item record
Abstract
Neurodevelopmental disorders such as fragile X syndrome (FXS) result in lifelong cognitive and behavioural deficits and represent a major public health burden. FXS is the most frequent monogenic form of intellectual disability and autism, and the underlying pathophysiology linked to its causal gene, FMR1, has been the focus of intense research. Key alterations in synaptic function thought to underlie this neurodevelopmental disorder have been characterized and rescued in animal models of FXS using genetic and pharmacological approaches. These robust preclinical findings have led to the implementation of the most comprehensive drug development programme undertaken thus far for a genetically defined neurodevelopmental disorder, including phase IIb trials of metabotropic glutamate receptor 5 (mGluR5) antagonists and a phase III trial of a GABA B receptor agonist. However, none of the trials has been able to unambiguously demonstrate efficacy, and they have also highlighted the extent of the knowledge gaps in drug development for FXS and other neurodevelopmental disorders. In this Review, we examine potential issues in the previous studies and future directions for preclinical and clinical trials. FXS is at the forefront of efforts to develop drugs for neurodevelopmental disorders, and lessons learned in the process will also be important for such disorders.
Date issued
2017-12
URI
https://hdl.handle.net/1721.1/126440
Department
Picower Institute for Learning and Memory
Journal
Nature Reviews Drug Discovery
Publisher
Springer Science and Business Media LLC
Citation
Berry-Kravis, E. M. "Drug development for neurodevelopmental disorders: lessons learned from fragile X syndrome." Nature Reviews Drug Discovery 17, 4 (December 2017): 280–299 © 2018 Macmillan Publishers Limited, part of Springer Nature
Version: Author's final manuscript
ISSN
1474-1776
1474-1784

Collections
  • MIT Open Access Articles

Browse

All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

My Account

Login

Statistics

OA StatisticsStatistics by CountryStatistics by Department
MIT Libraries homeMIT Libraries logo

Find us on

Twitter Facebook Instagram YouTube RSS

MIT Libraries navigation

SearchHours & locationsBorrow & requestResearch supportAbout us
PrivacyPermissionsAccessibility
MIT
Massachusetts Institute of Technology
Content created by the MIT Libraries, CC BY-NC unless otherwise noted. Notify us about copyright concerns.