Funding Summary
The goal of this study is to further evaluate whether the hormone, CART, is a viable therapeutic target for the treatment of the insatiable appetite associated with Prader Willi Syndrome (PWS). In this application, we propose to continue our studies through the following Aims: 1. determine if injection of CART can decrease appetite in obese Magel2-deficient rats; 2. evaluate whether Magel2-deficient rats have lower levels of pituitary hormones, including growth hormone, and whether injection of CART can elevate pituitary hormone secretion; 3. determine how Magel2 deficiency affects the biological rhythm of CART in brain tissues. Through these studies, we hope to provide additional verification that CART is a potential therapeutic target for appetite regulation in patients with PWS, and also provide evidence that CART could be used to normalize pituitary hormone secretion as well.
Dr. Theresa Strong, Director of Research Programs, explains the details of the project in this video clip.
Lay Abstract
The goal of this study is to further evaluate whether the hormone, CART, is a viable therapeutic target for the treatment of the insatiable appetite associated with Prader Willi Syndrome (PWS). In our project previously funded by FPWR, we found that administration of CART into a rat model of PWS (Magel2-deficient rats) led to a sustained reduction in appetite that was greater in the Magel2-deficient rats than in the control rats. We also found that Magel2-deficient rats were smaller than control rats, suggesting that these rats, like Magel2-deficient mice and children with PWS, have deficiencies in their pituitary hormones. In addition, we uncovered evidence of disrupted biological rhythms in the Magel2-deficient rats. In this application, we propose to continue our studies through the following Aims: 1. determine if injection of CART can decrease appetite in obese Magel2-deficient rats; 2. evaluate whether Magel2-deficient rats have lower levels of pituitary hormones, including growth hormone, and whether injection of CART can elevate pituitary hormone secretion; 3. determine how Magel2 deficiency affects the biological rhythm of CART in brain tissues. Through these studies, we hope to provide additional verification that CART is a potential therapeutic target for appetite regulation in patients with PWS, and also provide evidence that CART could be used to normalize pituitary hormone secretion as well. If the outcomes of these studies indicate that CART is a viable therapeutic target, the next steps would be to evaluate how long term treatment with CART affects appetite, body weight, and pituitary hormone secretion in Magel2-deficient rats. This would be complemented by biochemical studies to better understand the cellular dynamics of CART so that effective CART-based drugs could be designed. CART has been shown to reduce appetite and body weight in multiple rodent models of obesity, and has been proposed as a therapeutic target for the treatment of non-genetic human obesity. Thus, these studies would complement ongoing work in the field to ensure that patients with PWS are not excluded from the potential beneficial, anti-obesity effects of CART-based medications.
Funded Year:
2023
Awarded to:
Gina Yosten, PhD
Amount:
$162,000
Institution:
Saint Louis University
Researcher:
Gina Yosten, PhD
