Preventing hyperphagia in Prader Willi syndrome using an oligonucleotide

One of the most severe daily problems in Prader-Willi syndrome (PWS) is the inability to reach satiety after a meal, which leads to hyperphagia and obesity. The loss of expression of two small nucleolar RNA (snoRNA) clusters is a crucial genetic contributor to the disease. One of these snoRNAs (SNORD115) promotes the most active form of the serotonin receptor 2C (HTR2C). Activated HTR2C receptors in the arcuate nucleus inhibit food uptake. We developed an oligonucleotide (“oligo#5”) that similar to SNORD115 promotes the formation of the most active HTR2C receptor that localizes on the cell surface. Oligo#5 inhibits food uptake of fasted mice when delivered by intracerebroventricular (ICV) injection to the arcuate nucleus. We postulate that oligo#5 could be developed into an anti hyperphagia drug for Prader-Willi syndrome.