Hydrocephalus Complicating Intrathecal Antisense Oligonucleotide Therapy for Huntington's Disease.
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Peer-reviewed
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Abstract
Huntington’s disease (HD) is a genetic disorder caused by an expanded CAG repeat in the huntingtin gene, and although there are currently no disease-modifying treatments, there is much excitement about the prospect of treatments targeting huntingtin expression. In a phase I/2A trial of an antisense oligonucleotide (ASO) treatment (Tominersen), no serious adverse events were recorded, and there was a dose-dependent reduction in cerebrospinal fluid (CSF) huntingtin levels1. In an open-label extension (OLE) study, patients received monthly or bimonthly Tominersen, with preliminary data confirming the reduction in mutant huntingtin levels2. Here we report on a unique major adverse effect occurring during this OLE.
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Keywords
Humans, Huntingtin Protein, Huntington Disease, Hydrocephalus, Oligonucleotides, Antisense
Journal Title
Mov Disord
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Journal ISSN
0885-3185
1531-8257
1531-8257
Volume Title
36
Publisher
Wiley
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All rights reserved
Sponsorship
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Wellcome Trust (203151/Z/16/Z)
Medical Research Council (MC_PC_12009)
Medical Research Council (MC_PC_17230)
Wellcome Trust (203151/Z/16/Z)
Medical Research Council (MC_PC_12009)
Medical Research Council (MC_PC_17230)
Funding sources and conflict of interest – This trial was funded initially by Ionis and subsequently by Roche. The authors received no additional funding for this work and the authors declare that there are no conflicts of interest relevant to this work.
Financial disclosures - RAB is supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre - 146281 (the views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care) and MRC/WT Stem Cell Institute (203151/Z/16/Z).