Disease Progression in Multiple System Atrophy: The ASPIRE Multi-Modal Biomarker Study

Area of Science:

• Neurology
• Biomarker Research
• Neurodegenerative Diseases

Background:

• Multiple system atrophy (MSA) is a progressive neurodegenerative disorder.
• Early diagnosis and understanding disease progression are crucial for patient management.
• Candidate biomarkers require characterization in early-stage MSA.

Purpose of the Study:

• To characterize changes in candidate biomarkers in early multiple system atrophy (MSA).
• To identify baseline predictors of faster disease progression in MSA.
• To assess the utility of neuroimaging and plasma NfL in early MSA.

Main Methods:

• A 1-year prospective, multicenter study involving early MSA patients and healthy controls.
• Assessed clinical scores (UMSARS), 3T-MRI, DaT-SPECT, and plasma NfL.
• Analyzed changes from baseline to 6 and 12 months using mixed linear regression.

Main Results:

• Significant worsening of UMSARS scores and increased brainstem/cerebellar atrophy observed within 6 months.
• Decreased striatal specific binding ratio (SBR) was noted, with distinct patterns in MSA-P and MSA-C subtypes.
• Baseline brainstem/pons volume and SBR predicted clinical worsening; higher plasma NfL correlated with dropout and mortality risk.

Conclusions:

• Neuroimaging changes are detectable within 6 months in early MSA.
• Plasma NfL is a significant predictor of mortality and dropout risk in MSA.
• Longitudinal biomarker assessment offers valuable insights into MSA progression.