Currently, there are no objective biomarkers of hunger/satiety for PWS, which can be a barrier in PWS research. This study aims to develop an objective biomarker for altered satiety and hyperphagia in PWS using an eye-tracking method (measuring where a person is looking) to measure attentional bias (AB; increased attention) to food. Previously, this group showed that typical young adults show reduced AB to food after eating. The researchers hypothesize that people with PWS may not show a reduction in AB for food after eating. They will adapt their eye tracking protocol for individuals with PWS and test AB. If successful, they will have developed the first robust, objective biomarker of hunger/ satiety that could be used to monitor treatment effectiveness of new medicinal therapies for hyperphagia in PWS.
Dr. Theresa Strong, Director of Research Programs, shares details on this project in this short video clip.
Our study aims to develop a novel and objective biomarker for altered satiety and hyperphagia in PWS using an eye-tracking method to measure attentional bias (AB) to food. Eye-tracking is an experimental method that allows us to measure where a person is looking. ABs refer to increased attention (or looking) to particular stimuli that are of interest to the individual. A biomarker is an objective measure of a disease and can be used to measure a response to treatment. We previously showed that young adults look longer at food compared with non-food stimuli following a 4 hour fast compared with just after eating, i.e. their AB to food is reduced after eating. We propose that people with PWS will not show a reduction in AB for food after eating. Here, we aim to adapt and pilot our experimental protocol to be suitable for children and adolescents and adults with PWS. We will test the protocol in typically developing children and adolescents to determine if the same effects of satiety on AB seen in young adults are observed during development. We will then investigate if the satiety effect is altered in PWS, as we expect. To be considered a valid biomarker, a task like this must be valid (i.e., strongly related to satiety and hyperphagia) and reproducible, i.e. have good test-retest reliability. To demonstrate this we will relate the eye-tracking measures to scores on behavioural measures of hunger/ satiety and hyperphagia. Additionally, we will test a subgroup of children/ adolescents (with and without PWS) on two occasions, within two weeks, to assess if there is a strong relationship between the observed measures at each testing session. This research is important because there are no objective biomarkers of hunger/ satiety for PWS. This is a barrier for development of novel therapies for hyperphagia, which, if effective would be lifechanging for people with PWS and are a priority for their caregivers. The question, “what constitutes a meaningful improvement in hyperphagia for clinical trials in PWS?” was raised by the Federal Drug Agency, the regulatory authority in the USA. Thus, the PWS clinical trials consortium prioritized development of new objective outcome measures for hyperphagia, including eye-tracking methodologies. If successful, we will have developed the first robust, objective biomarker of hunger/ satiety that could be used to monitor treatment effectiveness of new medicinal therapies for hyperphagia in PWS. Following further multi-site testing, we will work with the PWS Clinical Trials Consortium to seek further guidance from the FDA regarding the possibility of incorporating this biomarker in clinical trials to further evaluate its usefulness. If useful, it has the potential to progress clinical trials of treatments for hyperphagia. To date, studies have shown ambiguous results because of a lack of a meaningful measure of hyperphagia. This means that some potentially beneficial therapies may not meet the FDA requirements to be considered an effective treatment. This project addresses a critical need for objective biomarkers for hyperphagia in PWS that can enhance therapeutic development and improved care for people with PWS.
Louise Gallagher, Ph.D.
Trinity Center for Health Sciences
Louise Gallagher, PhD