Osteoporosis is characterized by weakened and fragile bones and considered one of the major health abnormalities associated with Prader-Willi syndrome (PWS). This problem affects almost 90% of patients with PWS and has a negative impact on their quality of lives by causing physical and functional limitations that could also affect longevity. In order to develop effective therapeutic agents for this complication, an important question "Why PWS is largely associated with osteoporosis?" needs to be answered. The first step toward understanding this problem is to completely characterize the skeletal phenotype of mice that carry a genetic mutation similar to patients with PWS. Therefore, our first goal will be to evaluate the basal bone phenotype of Magel2 mutated mice and compare it to normal animals. Then, we will try to identify the biological mechanism(s) responsible for osteoporosis in PWS. Last, we will focus our interest on the endocannabinoid (eCB) system, which is known to modulate skeletal growth and remodeling. Among the various lipid substances that our body produces, eCBs, which act on the cellular receptor CB1, may lead to the development of osteoporosis in animal models. Consequently, we will test our hypothesis that overactivation of the eCB system is responsible for the increased bone resorption and/or decreased bone formation in PWS. Once completed, our experiments will highlight the contribution of the eCB system to the abnormal skeletal phenotype associated with PWS. This could further support the preclinical development and clinical testing of peripheral inhibitors against CB1 receptor for the treatment of osteoporosis in PWS.
Learn more about the importance of growth hormone therapy for PWS.
Magel2 Modulates Bone Remodeling and Mass in Prader-Willi Syndrome by Affecting Oleoyl Serine Levels and Activity. Baraghithy S, Smoum R, Drori A, Hadar R, Gammal A, Hirsch S, Attar-Namdar M, Nemirovski A, Gabet Y, Langer Y, Pollak Y, Schaaf CP, Rech ME, Gross-Tsur V, Bab I, Mechoulam R, Tam J. Journal of Bone and Mineral Research. 2018 Oct 22.
Yossi Tam, DMD, PhD
Hebrew University of Jerusalem, Israel