title: Huntington disease: natural history, biomarkers and prospects for therapeutics.
abstract: 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.
authors.affiliation: Division of Neurobiology, Johns Hopkins University, 600 North Wolfe Street, Baltimore, MD 21287, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ross
authors.affiliation: Seattle Children's Research Institute, USA.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Aylward
authors.affiliation: University College London, UK.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Wild
authors.affiliation: University of Iowa, USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Langbehn
authors.affiliation: University of Iowa, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Long
authors.affiliation: CHDI Management/CHDI Foundation, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Warner
authors.affiliation: University College London, UK.
authors.forename: Rachael I
authors.initials: RI
authors.lastname: Scahill
authors.affiliation: University of British Columbia, Canada.
authors.forename: Blair R
authors.initials: BR
authors.lastname: Leavitt
authors.affiliation: Monash University, Australia.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Stout
authors.affiliation: University of Iowa, USA.
authors.forename: Jane S
authors.initials: JS
authors.lastname: Paulsen
authors.affiliation: George-Huntington-Institute, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Reilmann
authors.affiliation: University of Zürich, Switzerland.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Unschuld
authors.affiliation: University of California, Los Angeles, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Wexler
authors.affiliation: Division of Neurobiology, Johns Hopkins University, 600 North Wolfe Street, Baltimore, MD 21287, USA.
authors.forename: Russell L
authors.initials: RL
authors.lastname: Margolis
authors.affiliation: University College London, UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Tabrizi
mesh_terms: D015415:Biomarkers; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D006816:Huntington Disease / Q000175:diagnosis / Q000473:pathology* / Q000523:psychology / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D059906:Neuroimaging; D011877:Radionuclide Imaging
chemical_list: D015415:Biomarkers