Huntington disease: natural history, biomarkers and prospects for therapeutics

CA Ross, EH Aylward, EJ Wild, DR Langbehn… - Nature Reviews …, 2014 - nature.com
CA Ross, EH Aylward, EJ Wild, DR Langbehn, JD Long, JH Warner, RI Scahill, BR Leavitt…
Nature Reviews Neurology, 2014nature.com
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 …
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.
nature.com