Gomez-Mancilla, Baltazar, Von Raison, Florian, Apostol, George, Ufer, Mike, Gasparini, Fabrizio, Berry Kravis, Elizabeth, Hageman, Randi and Jacquemont, Sébastien (2014) Development of mavoglurant and its potential for the treatment of fragile X syndrome. Expert Opinion on Investigational Drugs.

Abstract

Introduction—Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. With no curative treatment available, current approaches are aimed at symptom management. FXS is caused by silencing of the FMR1 gene, which encodes FMRP; loss of FMRP leads to the development of symptoms associated with FXS.
Areas covered—We examine the role of the metabotropic glutamate receptor 5 (mGluR5) in the pathophysiology of FXS, and its suitability as a therapeutic target with the potential to rescue the disease state. We also review evidence from preclinical studies of pharmacological interventions targeting mGluR5 in FXS. Finally, we assess the findings from clinical studies in FXS, in particular the use of the Aberrant Behaviour Checklist-Community Edition (ABC-C) and the recently developed ABC-C for FXS scale as clinical endpoints to assess disease modification in this patient population.
Expert opinion—There is cautious optimism for the successful treatment of the core behavioural and cognitive symptoms of FXS based on preclinical data in animal models and early studies in humans. However, the association between mGluR5 heightened responsiveness and the clinical phenotype in humans remains to be demonstrated and many questions on optimal treatment and outcome measures remain unanswered.

Item Type:	Article
Date Deposited:	26 Apr 2016 23:46
Last Modified:	26 Apr 2016 23:46
URI:	https://oak.novartis.com/id/eprint/11082