EJP RD JTC2022 - EJP RD - JTC 2022

Optical imaging as a diagnostic tool for monitoring brain function in X-linked rare disorders: from preclinical models to patients – IMAGINER

Submission summary

Fragile X syndrome (FXS) and Creatine Transporter Deficiency (CTD) are the two most common causes of X-linked intellectual disability. Despite their etiological heterogeneity, FXS and CTD share common clinical traits, such as cognitive and language dysfunction, autistic-like features, motor abnormalities and seizures. Also, analogous pathological substrates, including alterations of brain energetics, concur to the pathophysiology of both FXS and CTD. There is no cure for these disorders and the efficacy study of potential treatments is hindered by the scarcity of unbiased, quantitative, non-invasive biomarkers for monitoring brain function. This is an important problem, because the phenotypic observation of behavioural endpoints is highly prone to subjective bias, and the use of objective readouts is crucial to evaluate the therapeutic response to new drugs. Since abnormal hemodynamic responses (HR) to sensory stimulation have been reported in preclinical studies of FXS and CTD, the objective of this project is to exploit optical imaging techniques to devise a non-invasive biomarker for these disorders. We will use imaging of intrinsic optical signals (IOS) in animal models and functional near-infrared spectroscopy (fNIRS) in patients: these non-invasive tools, indeed, allow detecting the changes of hemoglobin species and local blood flow inside the brain, providing an indirect measure of neuronal activity. Since the study of the visual phenotype is a paradigmatic model to evaluate cortical processing in neurodevelopmental disorders, we will: 1. test whether visually-evoked IOS responses can discriminate between mutants and controls in animal models of FXS and CTD, predicting phenotype severity and treatment rescue effects; 2. investigate cellular, extracellular and molecular mechanisms underlying altered IOS; 3. assess whether visually-evoked fNIRS signals classify patients and healthy controls, showing a correlation with clinical outcomes. Based on solid preliminary results, this project will set the background for the use of optical imaging as a novel analytic tool to facilitate diagnostic monitoring and to predict the response to potential therapeutic strategies in FXS and CTD. Since fNIRS is non-invasive and user-friendly, our ultimate goal is to improve the pipeline of therapeutic development in neurodevelopmental disorders, demonstrating the importance to implement HR measures in clinical trials.

Project coordination

Laura Baroncelli ()

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.


HCL Hospices Civils de Lyon

Help of the ANR 1,400,768 euros
Beginning and duration of the scientific project: May 2023 - 36 Months

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