Effects of Ultrasound Sensory Neuromodulation in Multiple Mouse Models of Prader-Willi Syndrome

Funding Summary

Dr. Puleo and his team are investigating the use of peripheral ultrasound to modulate targets in the brain and impact energy balance and weight. They have strong preliminary data in several mouse/rat models of obesity and have performed early-stage clinical trials in healthy obese people. Here they will investigate mouse models of PWS to as a first step in determining the relevance of this therapeutic approach to PWS.

Dr. Theresa Strong, Director of Research Programs, shares details on this project in this short video clip. 

Lay Abstract

This project will determine if non-invasive ultrasound stimulation on peripheral/metabolic nerve pathways can drive therapeutic changes in neurochemistry and nerve activity within hypothalamic nuclei controlling hunger and metabolism. The work will be performed in models of Prader Willi Syndrome (PWS) to enable clinical translation of a currently available ultrasound system.
Currently, there is no cure or completely effective therapy for Prader-Willi Syndrome (PWS). Growth hormone therapy (GHT) remains the only FDA-approved treatment; however, while GHT improves height/stature, body composition, and mental/motor development, it does not improve obsessive and hyperphagic behaviors.
We have shown that our ultrasound stimulation technology can precisely modulate hypothalamic neurons controlling hunger and satiety (i.e., AGRP/NPY- and POMC-expressing neurons), potentially enabling a new way to therapeutically modulate food seeking behaviors and metabolism in diseases such as PWS. We have previously tested our technology on multiple non-PWS models of obesity with success, and show preliminary data that sensory stimulation therapeutically modulates neural circuits known to be affected by PWS. In this proposal, we will test this new form of non-invasive ultrasound therapy in two PWS specific animal models, and if successful our team maintains the ultrasound equipment and human feasibility/safety data with which to move this technology to the next step, that is phase I human trial testing.