Category: Huntington's Disease
Objective: To review studies for disease progression biomarkers published in HD and evaluate their methodological quality in a standardized manner.
Background: Huntington disease (HD) is a fatal autosomal dominant neurodegenerative condition that starts to manifest clinically around the 4th decade of life. There are promising novel genetic-based therapies under development intended to modify the disease trajectory. Valid biomarkers that can facilitate the development of such disease-modifying therapies are urgently needed. There are currently no studies that appraise the quality of research for validation of biomarkers in HD.
Method: A systematic review of all HD biomarker studies up to June 2020 was conducted. Each study was assessed for methodological quality using a 24- item standardized checklist. We completed a subgroup analyses based on year of publication and biomarker type (clinical, imaging, genetic, biochemical, and mixed biomarkers).
Results: We included 218 HD biomarker studies, of which 78 (35.8%) had a longitudinal design and 161 (74%) included a premanifest HD group. On average, 10 ± 3 items (out of 24) were rated as good quality. The checklist items that were more commonly rated as poor quality were: reporting of validity and reliability of assessments, sampling method, report of adverse events associated with the biomarker test, power calculation and appropriateness of study enrollment. Publications from 2016 to 2020 (mean score = 11.2 ± 2.3) had a better methodological quality than publications prior to 2016 (mean score = 9.9 ± 3.2; p = 0.035).
Conclusion: Overall, the reported methodological quality of the existing research on biomarkers for disease progression is low, which undermines the confidence of biomarkers use in drug development studies. It will be important to invest in better designed studies to support the use of biomarkers as valid drug development tools.
To cite this abstract in AMA style:
H. Tang, T. van Eimeren, C. Sampaio, T. Mestre. Validation of biomarkers in Huntington’s disease to support the development of disease-modifying therapies: a systematic review and critical appraisal scheme [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/validation-of-biomarkers-in-huntingtons-disease-to-support-the-development-of-disease-modifying-therapies-a-systematic-review-and-critical-appraisal-scheme/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/validation-of-biomarkers-in-huntingtons-disease-to-support-the-development-of-disease-modifying-therapies-a-systematic-review-and-critical-appraisal-scheme/