Huntington disease: natural history, biomarkers and prospects for therapeutics

被引：717

作者：

Ross, Christopher A. ^{[1
]}

Aylward, Elizabeth H. ^{[2
]}

Wild, Edward J. ^{[3
]}

Langbehn, Douglas R. ^{[4
]}

Long, Jeffrey D. ^{[4
]}

Warner, John H. ^{[5
]}

Scahill, Rachael I. ^{[3
]}

Leavitt, Blair R. ^{[6
]}

Stout, Julie C. ^{[7
]}

Paulsen, Jane S. ^{[4
]}

Reilmann, Ralf ^{[8
]}

Unschuld, Paul G. ^{[9
]}

Wexler, Alice ^{[10
]}

Margolis, Russell L. ^{[1
]}

Tabrizi, Sarah J. ^{[3
]}

机构：

[1] Johns Hopkins Univ, Div Neurobiol, Baltimore, MD 21287 USA

[2] Seattle Childrens Res Inst, Seattle, WA USA

[3] UCL, London WC1E 6BT, England

[4] Univ Iowa, Iowa City, IA 52242 USA

[5] CHDI Fdn, CHDI Management, Los Angeles, CA USA

[6] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada

[7] Monash Univ, Clayton, Vic 3800, Australia

[8] George Huntington Inst, Munster, Germany

[9] Univ Zurich, CH-8006 Zurich, Switzerland

[10] Univ Calif Los Angeles, Los Angeles, CA USA

来源：

NATURE REVIEWS NEUROLOGY | 2014年 / 10卷 / 04期

关键词：

CAG-REPEAT LENGTH; AGE-OF-ONSET; BASAL GANGLIA VOLUME; WHITE-MATTER VOLUME; PRE-MANIFEST; FUNCTIONAL CONNECTIVITY; COGNITIVE DYSFUNCTION; CLINICAL PROGRESSION; CEREBROSPINAL-FLUID; METABOLIC NETWORK;

D O I：

10.1038/nrneurol.2014.24

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Huntington disease (HD) can be seen as a model neurodegenerative disorder, in that it is caused by a single genetic mutation and is amenable to predictive genetic testing, with estimation of years to predicted onset, enabling the entire range of disease natural history to be studied. Structural neuroimaging biomarkers show that progressive regional brain atrophy begins many years before the emergence of diagnosable signs and symptoms of HD, and continues steadily during the symptomatic or 'manifest' period. The continued development of functional, neurochemical and other biomarkers raises hopes that these biomarkers might be useful for future trials of disease-modifying therapeutics to delay the onset and slow the progression of HD. Such advances could herald a new era of personalized preventive therapeutics. We describe the natural history of HD, including the timing of emergence of motor, cognitive and emotional impairments, and the techniques that are used to assess these features. Building on this information, we review recent progress in the development of biomarkers for HD, and potential future roles of these biomarkers in clinical trials.

引用

页码：204 / 216

页数：13

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