Deciphering the role of olfaction in Prader-Willi Syndrome

Funding Summary

These researchers hypothesize that PWS is associated with changes in the perception of food odors, which may drive some aspects of hyperphagia. In this study, Drs. Steculorum and Tauber will examine the role of olfaction in both patients with PWS and a mouse model of PWS, and will explore how one potential treatment, oxytocin, impacts the olfactory system. 

Dr. Theresa Strong, Director of Research Programs, explains the details of this project in this video clip.

Lay Abstract

The smell of food is a very important aspect of our eating habits that plays an important role in controlling food choices and preferences. Researchers have shown that food odours can initiate several changes in the body such as the release of hormones that give the signal to decrease food intake or the activation of cells in the brain that can also decrease feeding. The recent Covid-19 pandemic has notably increased our awareness of the critical importance of the sense of smell in regulating appetite and food decisions, as people suffering from anosmia due to Covid-19 report strong alterations in their eating habits. To date, the influence of the sense of smell on hyperphagia in Prader-Willi Syndrome remains unexplored. Based on this important role of the sense of smell in feeding and observations from clinicians, we hypothesized that PWS is associated with changes in the perception of food odours that might play a very important role in feeding in PWS. Our preliminary work revealed that PWS is associated with increased activation of specific brain regions in response to food odours. In this proposal, we aim to join forces with an expert clinician leading a PWS reference centre in France and an expert in neurodevelopmental biology in Germany. We propose to study the role of olfaction in patients with PWS and a pre-clinical mouse model of PWS. Further, because oxytocin is well known to control the formation of the olfactory system, we hypothesize that the beneficial action of oxytocin might be partly triggered by its effects on the development of brain regions important for the sense of smell. 

Because food odours have such strong effects on food preference and satiety, and our pilot experiments revealed increased food-odour sensitivity in PWS, we strongly believe that further characterization of the influence of the sense of smell in PWS might bring critical knowledge into PWS. As food odours are directly part of our environment, we believe that our proposal will have direct implications for patients with PWS. Indeed, our work might advocate for the individual design an optimal sensory environment during meals that might promote satiety or decrease hyperphagia. Because this proposal is led in collaboration with an expert clinician, the outcomes from our study will be directly implemented and tested in children and adults with PWS. Further, in the longer term, our work will also identify mechanisms at the origin of this food-odour hypersensitivity that could be the target of novel therapeutic intervention. Our proposal also includes a test in a mouse model of PWS aiming at understanding the exact changes occurring in specific cells in the nose or brain that receive and transmit information about food odours to the rest of the brain. Pinpointing important mechanisms by which PWS genes can influence the sense of smell will provide new directions for the treatment of PWS. In particular, nowadays, many drugs are applied intra-nasally, a simple and non-invasive way to administer treatment easily and efficiently as early as in newborns. Our mid-term goal is to test some of the pathways identified in this proposal in a mouse model of PWS.