title: Antisense oligonucleotides in therapy for neurodegenerative disorders.
abstract: Antisense oligonucleotides are synthetic single stranded strings of nucleic acids that bind to RNA and thereby alter or reduce expression of the target RNA. They can not only reduce expression of mutant proteins by breakdown of the targeted transcript, but also restore protein expression or modify proteins through interference with pre-mRNA splicing. There has been a recent revival of interest in the use of antisense oligonucleotides to treat several neurodegenerative disorders using different approaches to prevent disease onset or halt disease progression and the first clinical trials for spinal muscular atrophy and amyotrophic lateral sclerosis showing promising results. For these trials, intrathecal delivery is being used but direct infusion into the brain ventricles and several methods of passing the blood brain barrier after peripheral administration are also under investigation.
authors: Department of Human Genetics, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The Netherlands. Electronic address: m.m.evers@lumc.nl.
authors: Melvin M
authors: MM
authors: Evers
authors: Department of Human Genetics, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The Netherlands. Electronic address: l.j.a.toonen@lumc.nl.
authors: Lodewijk J A
authors: LJ
authors: Toonen
authors: Department of Human Genetics, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The Netherlands. Electronic address: w.vanroon@lumc.nl.
authors: Willeke M C
authors: WM
authors: van Roon-Mom
mesh_terms: D017398:Alternative Splicing / Q000187:drug effects / Q000235:genetics; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D016503:Drug Delivery Systems; D018390:Gene Targeting; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
chemical_list: D016376:Oligonucleotides, Antisense
keywords: Allele-specific reduction; Blood brain barrier; Genetic therapies; Neurodegenerative disorders; RNase H-mediated degradation; Splicing modulation; Translational blockage