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

Détails

ID Serval
serval:BIB_2B2D264EDE75
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Institution
Titre
Drug development for neurodevelopmental disorders: lessons learned from fragile X syndrome.
Périodique
Nature reviews. Drug discovery
Auteur(s)
Berry-Kravis E.M., Lindemann L., Jønch A.E., Apostol G., Bear M.F., Carpenter R.L., Crawley J.N., Curie A., Des Portes V., Hossain F., Gasparini F., Gomez-Mancilla B., Hessl D., Loth E., Scharf S.H., Wang P.P., Von Raison F., Hagerman R., Spooren W., Jacquemont S.
ISSN
1474-1784 (Electronic)
ISSN-L
1474-1776
Statut éditorial
Publié
Date de publication
04/2018
Peer-reviewed
Oui
Volume
17
Numéro
4
Pages
280-299
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
Publication Status: ppublish
Résumé
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 <sub>B</sub> 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.
Mots-clé
Animals, Clinical Trials as Topic, Drug Development/methods, Drug Evaluation, Preclinical, Fragile X Syndrome/drug therapy, Humans, Neurodevelopmental Disorders/drug therapy, Neurotransmitter Agents/pharmacology, Neurotransmitter Agents/therapeutic use, Randomized Controlled Trials as Topic
Pubmed
Web of science
Création de la notice
14/12/2017 18:08
Dernière modification de la notice
20/08/2019 13:10
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