Article (Scientific journals)
Modelling the natural history of Huntingtons disease progression
Kuan, William; Kasis, Andrea; Yuan, Ye et al.
2014In BMJ Open
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Abstract :
[en] Background: The lack of reliable biomarkers to track disease progression is a major problem in clinical research of chronic neurological disorders. Using Huntington’s disease (HD) as an example, we describe a novel approach to model HD and show that the progression of a neurological disorder can be predicted for individual patients. Methods : Starting with an initial cohort of 343 patients with HD that we have followed since 1995, we used data from 68 patients that satisfied our filtering criteria to model disease progression, based on the Unified Huntington’s Disease Rating Scale (UHDRS), a measure that is routinely used in HD clinics worldwide. Results : Our model was validated by: (A) extrapolating our equation to model the age of disease onset, (B) testing it on a second patient data set by loosening our filtering criteria, (C) cross-validating with a repeated random subsampling approach and (D) holdout validating with the latest clinical assessment data from the same cohort of patients. With UHDRS scores from the past four clinical visits (over a minimum span of 2 years), our model predicts disease progression of individual patients over the next 2 years with an accuracy of 89–91%. We have also provided evidence that patients with similar baseline clinical profiles can exhibit very different trajectories of disease progression. Conclusions : This new model therefore has important implications for HD research, most obviously in the development of potential disease-modifying therapies. We believe that a similar approach can also be adapted to model disease progression in other chronic neurological disorders.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Systems Control (Goncalves Group)
Disciplines :
Human health sciences: Multidisciplinary, general & others
Author, co-author :
Kuan, William
Kasis, Andrea
Yuan, Ye
Mason, S
Lazar, A
Barker, Roger
Goncalves, Jorge ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
External co-authors :
yes
Language :
English
Title :
Modelling the natural history of Huntingtons disease progression
Publication date :
December 2014
Journal title :
BMJ Open
ISSN :
2044-6055
Publisher :
BMJ Publishing Group Ltd, London, United Kingdom
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
the Cotswold Trust, the Rosetrees Trust, donations to the Huntington’s disease clinic in the John van Geest Centre for Brain Repair and an NIHR award of the Biomedical Research Centre—Cambridge University NHS Foundation Trust.
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