title: The prospect of molecular therapy for Angelman syndrome and other monogenic neurologic disorders.
abstract: BACKGROUND
  Angelman syndrome is a monogenic neurologic disorder that affects 1 in 15,000 children, and is characterized by ataxia, intellectual disability, speech impairment, sleep disorders, and seizures. The disorder is caused by loss of central nervous system expression of UBE3A, a gene encoding a ubiquitin ligase. Current treatments focus on the management of symptoms, as there have not been therapies to treat the underlying molecular cause of the disease. However, this outlook is evolving with advances in molecular therapies, including artificial transcription factors a class of engineered DNA-binding proteins that have the potential to target a specific site in the genome.
  
  
  RESULTS
  Here we review the recent progress and prospect of targeted gene expression therapies. Three main issues that must be addressed to advance toward human clinical trials are specificity, toxicity, and delivery.
  
  
  CONCLUSIONS
  Artificial transcription factors have the potential to address these concerns on a level that meets and in some cases exceeds current small molecule therapies. We examine the possibilities of such approaches in the context of Angelman syndrome, as a template for other single-gene, neurologic disorders.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Bailus
authors.affiliation: Genome Center, MIND Institute, and Department of Biochemistry and Molecular Medicine, University of California, Davis, CA 95616, USA. djsegal@ucdavis.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Segal
mesh_terms: D017204:Angelman Syndrome / Q000188:drug therapy* / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases