• W L Kuan, A Kasis, Y Yuan, S L Mason, A S Lazar, R A Barker, and J Goncalves.
• Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK.
• J. Neurol. Neurosurg. Psychiatr. 2015 Oct 1;86(10):1143-9.

BackgroundThe 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.MethodsStarting 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.ResultsOur 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.ConclusionsThis 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.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

20 keywords...

hide…