000			01921 am a22003013u 4500
042			_adc
100	1	0	_aTabrizi, Sarah J _eauthor _91227
700	1	0	_aEstevez-Fraga, Carlos _eauthor _91228
700	1	0	_avan Roon-Mom, Willeke M.C. _eauthor _91229
700	1	0	_aFlower, Michael D _eauthor _91230
700	1	0	_aScahill, Rachael I _eauthor _91231
700	1	0	_aWild, Ed J _eauthor _91232
700	1	0	_aMuñoz-Sanjuan, Ignacio _eauthor _91233
700	1	0	_aSampaio, Cristina _eauthor _91234
700	1	0	_aRosser, Anne E _eauthor _91235
700	1	0	_aLeavitt, Blair R. _eauthor _91236
245	0	0	_aPotential disease modifying therapies for Huntington's disease, lessons learned and future opportunities
260			_c2022-07-01.
500			_a/pmc/articles/PMC7613206/
500			_a/pubmed/35716694
520			_aHuntington's disease is the most frequent autosomal dominant neurodegenerative disorder, for which we have no approved disease-modifying treatments. The molecular pathogenesis of Huntington's disease is complex, with toxicity arising from full length expanded huntingtin and N-terminal fragments of huntingtin, which are both prone to misfolding due to proteolysis, from aberrant intron-1 splicing, and from somatic expansion of the CAG repeat in the HTT gene. Potential therapies for Huntington's disease include those targeting huntingtin DNA and RNA, clearance of huntingtin protein, DNA repair pathways, and other treatment strategies targeting inflammation and cell replacement. The early termination of the tominersen antisense oligonucleotide trials sent a strong signal that it is timely to reflect on lessons learned, where the field stands now, and our challenges and opportunities for the future.
540			_a
546			_aen
690			_aArticle
655	7		_aText _2local
786	0		_nLancet Neurol
856	4	1	_uhttp://dx.doi.org/10.1016/S1474-4422(22)00121-1 _zConnect to this object online.
999			_c781 _d781