Profiles of patients at early stages of Huntington’s disease based on the routine biological markers and the disease progression

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BACKGROUND: Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. Many studies attempt, besides age and CAG, to understand the factors that impact disease progression. Biological tests measuring several metabolic and inflammatory factors are frequently performed in outpatients, but their relation with disease progression is unknown. This study aims to evaluate the association between routine biological profiles at the early manifest stage of HD and subsequent disease progression. METHODS: From 2936 participants, the SPOT-HD database (combination of French part of REGISTRY, BIO-HD and REPAIR-HD), we selected 227 HD mutation carriers at an early stage of HD (HD-ISS stage 2 and CAP < 150), having both longitudinal measurements of routine blood biomarkers and clinical progression assessed using the Unified Huntington's Disease Rating Scale. Identification of biological routine profiles was performed using an iterative non-parametric model selection with dimensionality reduction algorithm, k-means clustering, LASSO regression, and Random Forest. Disease progression of each profile was estimated using generalized additive modeling. RESULTS: Three profiles were identified with distinct trajectories of HD progression (p < 0.001). The Rapid-Progression Profile with relatively higher levels of triglycerides, liver enzymes, and body mass index, coupled with lower high-density lipoprotein (HDL) cholesterol levels was noted. The Intermediate-Progression profile with relatively higher HDL levels, lower triglycerides, and inflammatory and liver markers in the lower end of the normal range was noticed. The Slow-Progression Profile with a tendency for higher T4 and creatinine levels, a greater concentration of lymphocytes than in other profiles, and low HDL despite normal triglycerides were studied. CONCLUSION: Biological routine profiles may help anticipating HD progression, thus facilitating personalized medicine approaches. These findings suggest that routine metabolic and inflammatory markers may be useful for patient follow-up in HD.

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