Modelling the natural history of Huntington's disease progression

Kuan, W L, Kasis, A, Yuan, Y, Mason, S L, Lazar, A S, Barker, R A and Goncalves, J (2015) Modelling the natural history of Huntington's disease progression. Journal of Neurology, Neurosurgery and Psychiatry, 86 (10). pp. 1143-1149. ISSN 0022-3050

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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.

Item Type: Article
Additional Information: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
Uncontrolled Keywords: age of onset,cohort studies,disability evaluation,disease progression,female,humans,huntington disease,male,middle aged,biological models,reproducibility of results,trinucleotide repeats
Faculty \ School: Faculty of Medicine and Health Sciences > School of Health Sciences
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Dementia & Complexity in Later Life
Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health
Depositing User: Pure Connector
Date Deposited: 07 Dec 2016 00:07
Last Modified: 19 Oct 2023 01:52
DOI: 10.1136/jnnp-2014-308153

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