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

Fragile X syndrome (FXS) and Creatine Transporter Deficiency (CTD) are the two most common causes of X-linked intellectual disability.

FXS and CTD share common clinical traits, such as cognitive dysfunction, autistic-like features, motor abnormalities and seizures. They also have similar pathophysiology, including alterations of brain energetics.

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 behavioural endpoints is subjective, and the use of objective measures is crucial to assess efficacy of 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 allow sensitive detection the changes of hemoglobin species and local blood flow inside the brain, thus providing an indirect measure of neuronal activity.

We will: 1) test IOS responses between mutants and controls in animal models of FXS and CTD; 2) investigate molecular mechanisms underlying altered IOS; 3) validate the clinical relevance using fNIRS in patient population.