Electroretinography and contrast sensitivity, complementary translational biomarkers of sensory deficits in the visual system of individuals with Fragile X Syndrome [post]

Olivier Perche, Fabien Lesne, Alain Patat, Susanne Raab, Roy Twyman, Robert H. Ring, Sylvain Briault
2021 unpublished
Background: Disturbances in sensory function are considered as an important clinical feature of individuals with neurodevelopmental disorders such as Fragile X syndrome (FXS). Evidence also directly connects sensory abnormalities with the clinical expression of behavioral impairments in individuals with FXS, thus elevating interest in sensory function as a clinical target for therapeutics development. Using electroretinography (ERG) and contrast sensitivity (CS), we previously reported the
more » ... nce of sensory deficits in the visual system of the Fmr1-/y genetic mouse model of FXS. The goals of this study were two-fold: 1) assess the feasibility of measuring ERG and CS as a biomarker in individuals with FXS, and 2) investigate whether the deficits in ERG and CS originally discovered in Fmr1-/y mice were translatable to humans with FXS. Methods: Both ERGs and CS were measured in a cohort of individuals with FXS (n=20, 18-45 yrs) and age-matched healthy controls (n=20, 18-45 yrs). Under light-adapted conditions, and using both single flash and flicker (repeated train of flashes) stimulation protocols, retinal function was recorded from individual subjects using a portable, handheld, full field flash ERG device (RETeval®, LKC Technologies Inc, Gaithersburg, MD, USA). CS was assessed in each subject using the LEA SYMBOLS® low-contrast test (Good-Lite, Elgin, IL, USA). Results: Data recording was successfully completed for ERG and assessment of CS in most individuals from both cohorts demonstrating the feasibility of these methods for use in the FXS population. Similar to previously reported findings from the Fmr1-/y genetic mouse model of FXS, abnormalities in both ERG waveform and CS were observed in FXS. Conclusions: This study demonstrates the feasibility of using ERG and CS for assessing the visual system in FXS and establishes the translatability of the Fmr1-/y mice phenotype to individuals with FXS. By including electrophysiological and functional readouts, the results of this study suggest the utility of both ERG and CS (ERG-CS) as complimentary translational biomarkers for characterizing sensory abnormalities found in FXS, with potential applications to the clinical development of novel therapeutics that target sensory function abnormalities to treat core symptomatology in FXS.Trial Registration: ID-RCB number 2019-A01015-52 registered on the 05/17/2019.
doi:10.21203/rs.3.rs-389870/v1 fatcat:hdv3uwy3q5b7zh7toa6yzoxeca