Effects of mavoglurant on visual attention and pupil reactivity while viewing photographs of faces in Fragile X Syndrome

David R Hessl, Danielle J Harvey, Stephanie Sansone, Crystal Crestodina, Jamie Chin, Reshma Joshi, Randi J Hagerman, Elizabeth Berry-Kravis

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background Numerous preclinical studies have supported the theory that enhanced activation of mGluR5 signaling, due to the absence or reduction of the FMR1 protein, contributes to cognitive and behavioral deficits in patients with fragile X syndrome (FXS). However multiple phase 2 controlled trials in patients with FXS have failed to demonstrate efficacy of compounds that negatively modulate mGluR5, including two phase 2b randomized controlled trials (RCT) of mavoglurant (AFQ056, Novartis Pharma AG), when the primary measures of interest were behavioral ratings. This has cast some doubt onto the translation of the mGluR5 theory from animal models to humans with the disorder. Methods We evaluated social gaze behavior–a key phenotypic feature of the disorder—and sympathetic nervous system influence on pupil size using a previously-validated eye tracking paradigm as a biobehavioral probe, in 57 adolescent or adult patients with FXS at baseline and following three months of blinded treatment with one of three doses of mavoglurant or placebo, within the context of the AFQ056 RCTs. Results Patients with FXS treated with mavoglurant demonstrated increased total absolute looking time and number of fixations to the eye region while viewing human faces relative to baseline, and compared to those treated with placebo. In addition, patients had greater pupil reactivity to faces relative to baseline following mavoglurant treatment compared to placebo. Discussion The study shows that negative modulation of mGluR5 activity improves eye gaze behavior and alters sympathetically-driven reactivity to faces in patients with FXS, providing preliminary evidence of this drug’s impact on behavior in humans with the disorder.

Original languageEnglish (US)
Article numbere0209984
JournalPLoS One
Volume14
Issue number1
DOIs
StatePublished - Jan 1 2019

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Fragile X Syndrome
Pupil
photographs
students
placebos
eyes
Placebos
sympathetic nervous system
Sympathetic Nervous System
Neurology
human behavior
mavoglurant
Animals
Randomized Controlled Trials
Animal Models
animal models
Chemical activation
Modulation
drugs
Therapeutics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Effects of mavoglurant on visual attention and pupil reactivity while viewing photographs of faces in Fragile X Syndrome. / Hessl, David R; Harvey, Danielle J; Sansone, Stephanie; Crestodina, Crystal; Chin, Jamie; Joshi, Reshma; Hagerman, Randi J; Berry-Kravis, Elizabeth.

In: PLoS One, Vol. 14, No. 1, e0209984, 01.01.2019.

Research output: Contribution to journalArticle

Hessl, David R ; Harvey, Danielle J ; Sansone, Stephanie ; Crestodina, Crystal ; Chin, Jamie ; Joshi, Reshma ; Hagerman, Randi J ; Berry-Kravis, Elizabeth. / Effects of mavoglurant on visual attention and pupil reactivity while viewing photographs of faces in Fragile X Syndrome. In: PLoS One. 2019 ; Vol. 14, No. 1.
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