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

Details

Serval ID
serval:BIB_2B2D264EDE75
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Drug development for neurodevelopmental disorders: lessons learned from fragile X syndrome.
Journal
Nature reviews. Drug discovery
Author(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
Publication state
Published
Issued date
04/2018
Peer-reviewed
Oui
Volume
17
Number
4
Pages
280-299
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
Publication Status: ppublish
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 <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.
Keywords
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
Create date
14/12/2017 18:08
Last modification date
20/08/2019 13:10
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