title: Delivering a disease-modifying treatment for Huntington's disease.
abstract: Huntington's disease (HD) is an incurable genetic neurodegenerative disorder that leads to motor and cognitive decline. It is caused by an expanded polyglutamine tract within the Huntingtin (HTT) gene, which translates into a toxic mutant HTT (muHTT) protein. Although no cure has yet been discovered, novel therapeutic strategies, such as RNA interference (RNAi), antisense oligonucleotides (ASOs), ribozymes, DNA enzymes, and genome-editing approaches, aimed at silencing or repairing the muHTT gene hold great promise. Indeed, several preclinical studies have demonstrated the utility of such strategies to improve HD neuropathology and symptoms. In this review, we critically summarise the main advances and limitations of each gene-silencing technology as an effective therapeutic tool for the treatment of HD.
authors.affiliation: Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
authors.forename: Bruno M D C
authors.initials: BM
authors.lastname: Godinho
authors.affiliation: Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork, Ireland.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Malhotra
authors.affiliation: Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork, Ireland.
authors.forename: Caitriona M
authors.initials: CM
authors.lastname: O'Driscoll
authors.affiliation: Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Laboratory of Neurogastroenterology, Alimentary Pharmabiotic Centre, Cork, Ireland. Electronic address: j.cryan@ucc.ie.
authors.forename: John F
authors.initials: JF
authors.lastname: Cryan
mesh_terms: D000483:Alleles; D000818:Animals; D020868:Gene Silencing; D015894:Genome, Human; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins