title: Pharmacological therapies for Angelman syndrome.
abstract: Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by a loss of the maternally inherited UBE3A; the paternal UBE3A is silenced in neurons by a mechanism involving an antisense transcript (UBE3A-AS). We reviewed the published information on clinical trials that have been completed as well as the publicly available information on ongoing trials of therapies for AS. Attempts at hypermethylating the maternal locus through dietary compounds were ineffective. The results of a clinical trial using minocycline as a matrix metalloproteinase-9 inhibitor were inconclusive; another clinical trial is underway. Findings from a clinical trial using L-dopa to alter phosphorylation of calcium/calmodulin-dependent kinase II are awaited. Topoisomerase inhibitors and antisense oligonucleotides are being developed to directly inhibit UBE3A-AS. Other strategies targeting specific pathways are briefly discussed. We also reviewed the medications that are currently used to treat seizures and sleep disturbances, which are two of the more debilitating manifestations of AS.
authors.affiliation: Division of Genetics and Genomics, Boston Children's Hospital; Harvard Medical School, Boston, MA, USA.
authors.forename: Wen-Hann
authors.initials: WH
authors.lastname: Tan
authors.affiliation: Department of Pediatrics, University of California, San Diego, CA, USA. lbird@rchsd.org.|Division of Genetics/Dysmorphology, Rady Children's Hospital San Diego, 3020 Children's Way, # 5031, 92123, San Diego, CA, USA. lbird@rchsd.org.
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Bird
mesh_terms: D017204:Angelman Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D020868:Gene Silencing; D007980:Levodopa / Q000627:therapeutic use; D051379:Mice; D008911:Minocycline / Q000627:therapeutic use; D020320:Oligoribonucleotides, Antisense / Q000627:therapeutic use; D012640:Seizures / Q000188:drug therapy; D012893:Sleep Wake Disorders / Q000188:drug therapy; D059003:Topoisomerase Inhibitors / Q000627:therapeutic use; D044767:Ubiquitin-Protein Ligases
chemical_list: D020320:Oligoribonucleotides, Antisense; D059003:Topoisomerase Inhibitors; D007980:Levodopa; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases; D008911:Minocycline
keywords: Angelman syndrome; Clinical trial; Mouse model; Therapeutic; Therapy