{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T22:28:34Z","timestamp":1788560914812,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,8,27]],"date-time":"2014-08-27T00:00:00Z","timestamp":1409097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2014,9,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The idea to lower mutant huntingtin is especially appealing in Huntington's disease (HD). It is autosomal dominant, so that expression of the mutant allele causes the disease. Advances in RNA and gene regulation provide foundations for the huntingtin gene (both normal and mutant alleles) and possibly the mutant allele only. There is much preclinical animal work to support the concept of gene and RNA silencing, but, to date, no clinical studies have been attempted in HD. Preventing expression of mutant huntingtin protein is at the cusp for a human trial. Antisense oligonucleotides delivered to patients with amyotrophic lateral sclerosis have been well tolerated; small RNAs administered to rodent and nonhuman primate brain knocked down huntingtin messenger RNA (mRNA); short\u2010hairpin complementary DNA of microRNAs can be expressed in adeno\u2010associated virus to provide long\u2010term silencing of huntingtin mRNA and protein. We expect that these approaches will be ready for clinical studies in the near future, once safety has been validated. Our understanding of gene editing\u2014changing the huntingtin gene itself\u2014is rapidly progressing. Harnessing our knowledge of transcription and translation should push scientific creativity to new and exciting advances that overcome the lethality of the mutant gene in HD. \u00a9 2014 International Parkinson and Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.26020","type":"journal-article","created":{"date-parts":[[2014,8,27]],"date-time":"2014-08-27T12:11:37Z","timestamp":1409141497000},"page":"1455-1461","source":"Crossref","is-referenced-by-count":72,"title":["Huntingtin\u2010lowering strategies in Huntington's disease: Antisense oligonucleotides, small RNAs, and gene editing"],"prefix":"10.1002","volume":"29","author":[{"given":"Neil","family":"Aronin","sequence":"first","affiliation":[{"name":"Department of Medicine and RNA Therapeutics Institute University of Massachusetts Medical School Worcester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"DiFiglia","sequence":"additional","affiliation":[{"name":"Department of 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