title: Development of mavoglurant and its potential for the treatment of fragile X syndrome.
abstract: BACKGROUND
  Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. With no curative treatment available, current therapeutic approaches are aimed at symptom management. FXS is caused by silencing the FMR1 gene, which encodes FMRP; as loss of FMRP leads to the development of symptoms associated with FXS.
  
  
  METHODS
  In this evaluation, the authors examine the role of the metabotropic glutamate receptor 5 (mGluR5) in the pathophysiology of FXS, and its suitability as a target for rescuing the disease state. Furthermore, the authors review the evidence from preclinical studies of pharmacological interventions targeting mGluR5 in FXS. Lastly, the authors assess the findings from clinical studies in FXS, in particular the use of the Aberrant Behavior 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.
  
  
  CONCLUSIONS
  There is cautious optimism for the successful treatment of the core behavioral 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. Many questions regarding the optimal treatment and outcome measures of FXS remain unanswered.
authors.affiliation: Novartis Institutes for BioMedical Research Basel, Forum 1 , Novartis Campus, CH-4056 Basel , Switzerland +41 61 324 0164 ; +41 61 324 8913 ; baltazar.gomezmancilla@novartis.com.
authors.forename: Baltazar
authors.initials: B
authors.lastname: Gomez-Mancilla
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Berry-Kravis
authors.forename: Randi
authors.initials: R
authors.lastname: Hagerman
authors.forename: Florian
authors.initials: F
authors.lastname: von Raison
authors.forename: George
authors.initials: G
authors.lastname: Apostol
authors.forename: Mike
authors.initials: M
authors.lastname: Ufer
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Gasparini
authors.forename: Sébastien
authors.initials: S
authors.lastname: Jacquemont
mesh_terms: D000818:Animals; D005600:Fragile X Syndrome / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D007211:Indoles; D064529:Receptor, Metabotropic Glutamate 5; C581397:mavoglurant