Koval, Igor;
Dighiero-Brecht, Thomas;
Tobin, Allan J;
Tabrizi, Sarah J;
Scahill, Rachael I;
Tezenas du Montcel, Sophie;
Durrleman, Stanley;
(2022)
Forecasting individual progression trajectories in Huntington disease enables more powered clinical trials.
Scientific Reports
, 12
, Article 18928. 10.1038/s41598-022-18848-8.
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Abstract
Variability in neurodegenerative disease progression poses great challenges for the evaluation of potential treatments. Identifying the persons who will experience significant progression in the short term is key for the implementation of trials with smaller sample sizes. We apply here disease course mapping to forecast biomarker progression for individual carriers of the pathological CAG repeat expansions responsible for Huntington disease. We used data from two longitudinal studies (TRACK-HD and TRACK-ON) to synchronize temporal progression of 15 clinical and imaging biomarkers from 290 participants with Huntington disease. We used then the resulting HD COURSE MAP to forecast clinical endpoints from the baseline data of 11,510 participants from ENROLL-HD, an external validation cohort. We used such forecasts to select participants at risk for progression and compute the power of trials for such an enriched population. HD COURSE MAP forecasts biomarkers 5 years after the baseline measures with a maximum mean absolute error of 10 points for the total motor score and 2.15 for the total functional capacity. This allowed reducing sample sizes in trial up to 50% including participants with a higher risk for progression ensuring a more homogeneous group of participants.
| Type: | Article |
|---|---|
| Title: | Forecasting individual progression trajectories in Huntington disease enables more powered clinical trials |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41598-022-18848-8 |
| Publisher version: | https://doi.org/10.1038/s41598-022-18848-8 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Humans, Huntington Disease, Neurodegenerative Diseases, Longitudinal Studies, Cohort Studies, Biomarkers, Disease Progression |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10159667 |
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