The purpose of this study is to determine the safety and effectiveness of an experimental drug called ION582 in children and adults with Angelman syndrome. Angelman syndrome is a rare genetic condition resulting in severe developmental delays that include intellectual disability, limited speech, seizure disorder (epilepsy), motor problems, behavioral problems, and sleep disturbances. Angelman syndrome is caused by the lack of UBE3A protein, and ION582 is administered in the spinal subarachnoid space to unblock the paternal UBE3A gene so UBE3A protein can be produced. This study consists of a treatment evaluation period, long-term extension, and follow-up period. In the treatment evaluation portion of the study, participants will be assigned to receive either ION582 or placebo (inactive substance). Study procedures also include collection of blood and urine samples, as well as completion of assessments, questionnaires, and a seizure diary. Study participants who are assigned to the placebo group will start receiving the study drug after 15 months. The participants who are assigned to receiving the study drug will continue receiving it in the long-term extension.