Unraveling progression subtypes in people with Huntington's disease.

Autor: Raschka T; Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Schloss Birlinghoven, 53757 Sankt Augustin, Germany., Li Z; Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Schloss Birlinghoven, 53757 Sankt Augustin, Germany.; Bonn-Aachen International Center for IT, University of Bonn, Friedrich-Hirzebruch-Allee 6, 53115 Bonn, Germany., Gaßner H; Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.; Fraunhofer IIS, Fraunhofer Institute for Integrated Circuits IIS, Am Wolfsmantel 33, 91058 Erlangen, Germany., Kohl Z; Department of Neurology, University of Regensburg, Regensburg, Germany., Jukic J; Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.; Center for Rare Diseases Erlangen (ZSEER), University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany., Marxreiter F; Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.; Center for Movement Disorders, Passauer Wolf, 93333 Bad Gögging, Germany.; Center for Rare Diseases Erlangen (ZSEER), University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany., Fröhlich H; Department of Bioinformatics, Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), Schloss Birlinghoven, 53757 Sankt Augustin, Germany.; Bonn-Aachen International Center for IT, University of Bonn, Friedrich-Hirzebruch-Allee 6, 53115 Bonn, Germany.
Jazyk: angličtina
Zdroj: The EPMA journal [EPMA J] 2024 May 28; Vol. 15 (2), pp. 275-287. Date of Electronic Publication: 2024 May 28 (Print Publication: 2024).
DOI: 10.1007/s13167-024-00368-2
Abstrakt: Background: Huntington's disease (HD) is a progressive neurodegenerative disease caused by a CAG trinucleotide expansion in the huntingtin gene. The length of the CAG repeat is inversely correlated with disease onset. HD is characterized by hyperkinetic movement disorder, psychiatric symptoms, and cognitive deficits, which greatly impact patient's quality of life. Despite this clear genetic course, high variability of HD patients' symptoms can be observed. Current clinical diagnosis of HD solely relies on the presence of motor signs, disregarding the other important aspects of the disease. By incorporating a broader approach that encompasses motor as well as non-motor aspects of HD, predictive, preventive, and personalized (3P) medicine can enhance diagnostic accuracy and improve patient care.
Methods: Multisymptom disease trajectories of HD patients collected from the Enroll-HD study were first aligned on a common disease timescale to account for heterogeneity in disease symptom onset and diagnosis. Following this, the aligned disease trajectories were clustered using the previously published Variational Deep Embedding with Recurrence (VaDER) algorithm and resulting progression subtypes were clinically characterized. Lastly, an AI/ML model was learned to predict the progression subtype from only first visit data or with data from additional follow-up visits.
Results: Results demonstrate two distinct subtypes, one large cluster ( n  = 7122) showing a relative stable disease progression and a second, smaller cluster ( n  = 411) showing a dramatically more progressive disease trajectory. Clinical characterization of the two subtypes correlates with CAG repeat length, as well as several neurobehavioral, psychiatric, and cognitive scores. In fact, cognitive impairment was found to be the major difference between the two subtypes. Additionally, a prognostic model shows the ability to predict HD subtypes from patients' first visit only.
Conclusion: In summary, this study aims towards the paradigm shift from reactive to preventive and personalized medicine by showing that non-motor symptoms are of vital importance for predicting and categorizing each patients' disease progression pattern, as cognitive decline is oftentimes more reflective of HD progression than its motor aspects. Considering these aspects while counseling and therapy definition will personalize each individuals' treatment. The ability to provide patients with an objective assessment of their disease progression and thus a perspective for their life with HD is the key to improving their quality of life. By conducting additional analysis on biological data from both subtypes, it is possible to gain a deeper understanding of these subtypes and uncover the underlying biological factors of the disease. This greatly aligns with the goal of shifting towards 3P medicine.
Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00368-2.
Competing Interests: Competing interestsHolger Fröhlich has received grants from UCB and AbbVie outside this work. All other authors declare no competing interests.
(© The Author(s) 2024.)
Databáze: MEDLINE
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