title: Oligonucleotide therapeutic approaches for Huntington disease.
abstract: Huntington disease is an autosomal dominant neurodegenerative disorder caused by a toxic expansion in the CAG repeat region of the huntingtin gene. Oligonucleotide approaches based on RNAi and antisense oligonucleotides provide promising new therapeutic strategies for direct intervention through reduced production of the causative mutant protein. Allele-specific and simultaneous mutant and wild-type allele-lowering strategies are being pursued with local delivery to the brain, each with relative merits. Delivery remains a key challenge for translational success, especially with chronic therapy. The potential of disease-modifying oligonucleotide approaches for Huntington disease will be revealed as they progress into clinical trials.
authors.affiliation: Alnylam Pharmaceuticals Inc., Cambridge, Massachusetts, USA.
authors.forename: Dinah W Y
authors.initials: DW
authors.lastname: Sah
authors.forename: Neil
authors.initials: N
authors.lastname: Aronin
mesh_terms: D002986:Clinical Trials as Topic; D020868:Gene Silencing; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000473:pathology / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009841:Oligonucleotides / Q000627:therapeutic use*; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D034622:RNA Interference; D019680:Trinucleotide Repeat Expansion
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense