Metabotropic glutamate receptor 5 as drug target for Fragile X syndrome.

Autor: Scharf SH; Roche Pharmaceutical Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, 4070 Basel, Switzerland., Jaeschke G; Roche Pharmaceutical Research and Early Development, Small Molecules Research, Discovery Chemistry, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, 4070 Basel, Switzerland., Wettstein JG; Roche Pharmaceutical Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, 4070 Basel, Switzerland., Lindemann L; Roche Pharmaceutical Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, 4070 Basel, Switzerland. Electronic address: lothar.lindemann@roche.com.
Jazyk: angličtina
Zdroj: Current opinion in pharmacology [Curr Opin Pharmacol] 2015 Feb; Vol. 20, pp. 124-34. Date of Electronic Publication: 2014 Dec 02.
DOI: 10.1016/j.coph.2014.11.004
Abstrakt: Fragile X syndrome (FXS) is the most common monogenic form of inherited mental retardation caused by a trinucleotid repeat expansion and transcriptional shutdown of the FMR1 gene. FXS patients present a complex and often severe neuropsychiatric phenotype yet have mild somatic symptoms, normal life expectancies, and no indications of neurodegeneration. The therapeutic potential of mGlu5 inhibitors was proposed in the 'mGluR theory of FXS' based on early insights into the molecular pathophysiology of FXS. Studies in Fragile X mental retardation 1 (Fmr1) knock-out mice, a widely used disease model, demonstrated that mGlu5 inhibitors can correct a broad range of disease-related phenotypes. Recent clinical trials, however, with two different mGlu5 inhibitors (basimglurant and mavoglurant) showed no therapeutic benefit in FXS patients for reasons as yet unclear.
(Copyright © 2014 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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