Muscle MRI as an Imaging Biomarker of Muscle Damage in Patients With Spinal and Bulbar Muscular Atrophy.

BACKGROUND AND

OBJECTIVES

Spinal and bulbar muscular atrophy (SBMA) is a rare neuromuscular disorder without effective treatments available. There is an unmet need to identify biomarkers reflecting underlying disease processes and sufficiently responsive to detect slow changes to enable future clinical trials. Muscle MRI is a responsive measure of muscle volume and fat content, a pathologic hallmark of SBMA that precedes functional changes. We therefore assessed muscle MRI as a potential imaging biomarker for detecting change in SBMA severity.

METHODS

This was a noninterventional, longitudinal study enrolling patients with confirmed SBMA diagnosis and evidence of muscle fat replacement. All patients were assessed by MRI and clinical measures at baseline and at 6-month intervals for up to 18 months. Whole-body Dixon MRI scans were analyzed using AMRA Researcher, assessing 19 muscle groups bilaterally and quantifying lean muscle volume (LMV), muscle fat fraction (MFF), and muscle fat infiltration (MFI). Rate of change was calculated for whole-body and regional muscle composite measures. Key clinical outcome measures included the Spinal Bulbar Muscular Atrophy Functional Rating Scale (SBMAFRS) and 2-minute walk test (2MWT). Correlation between muscle MRI measures and clinical assessments was calculated using Spearman correlation analysis, and responsiveness to change was evaluated using standardized response mean (SRM).

RESULTS

We included 26 patients with a mean age of 57.6 ± 7.12 years (range:44-71 years), mean SBMAFRS 40.6 ± 3.85 (range:33-48), and a mean baseline 2MWT distance of 126.09 ± 39.83 m (range:39.0-194.0). The mean changes and (SRM) over 12 months in whole-body muscle MRI were LMV -4.38 ± 2.48% (-1.76), MFF 2.49 ± 1.38p.p. (1.81), and MFI 0.79 ± 0.51p.p. (1.55) (p < 0.001). Baseline whole-body LMV/MFF/MFI showed moderate correlation to SBMAFRS (r:0.46/-0.41/-0.51, respectively) and modified SBMAFRS (r:0.50/-0.63/-0.67, respectively). Thigh LMV/MFF/MFI showed moderate correlation to 2MWT (r: 0.73/-0.53/-0.55).

DISCUSSION: Consistent and reproducible decreases in whole-body and regional muscle LMV composites over time and increases in MFF and MFI were observed across SBMA patients. Baseline MRI assessments reflect disease severity correlating with SBMAFRS and 2MWT functional measures. SRM of muscle MRI was higher than SRMs of functional measures, indicating that muscle MRI is a responsive biomarker that tracks disease progression and potentially treatment effects in future clinical trials.