Multiple sclerosis (Houndmills, Basingstoke, England) · 2026
Longitudinal magnetic resonance spectroscopy study of metabolite changes over 2 years in relapsing and primary progressive multiple sclerosis treated with ocrelizumab.
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MacMillan Erin L, Russell-Schulz Bretta, Alejo Glaynel, Harp Christopher, Cameron Briana, Winger Ryan, Jia Sherman, Herman Ann, Kassam Jasmyne, Waine Michael, Vavasour Irene M, Cross Helen, Tam Roger, Traboulsee Anthony L, Carruthers Robert, Kolind Shannon H
Аннотация
BACKGROUND: Magnetic resonance spectroscopy (MRS) offers non-invasive assessments of neuron-oligodendrocyte coupling and neuroinflammation to monitor treatment response in multiple sclerosis (MS).
OBJECTIVE: To track changes in N-acetylaspartate and myo-inositol in relapsing MS (RMS) and primary progressive MS (PPMS) patients treated with ocrelizumab over 2 years.
METHODS: Single-voxel MRS at 3T was acquired at baseline in 10 healthy controls (HCs), and weeks 0, 12, 24, 52, and 96 in MS participants at a single center.
RESULTS: Baseline myo-inositol was higher in PPMS than RMS (p = 0.047) and HC (p = 0.001), and correlated with disability across both MS groups (r = 0.57, p = 0.0006). Following treatment with ocrelizumab, both RMS and PPMS demonstrated declines in myo-inositol over time, returning toward HC levels (RMS p = 0.016; PPMS p = 0.004). Conversely, N-acetylaspartate was not different between groups and remained stable over time.
CONCLUSION: Ocrelizumab treatment is associated with declining myo-inositol levels measured by MRS in both RMS and PPMS. Myo-inositol offers a unique biomarker to track resolution of gliosis and reactive microglia with treatment. Furthermore, the relationship between a higher concentration of myo-inositol and greater disability across both MS subtypes at baseline supports the presence of "smouldering inflammation" as a disease process across the spectrum of MS.
CLINICAL TRIAL: Sub-study of the Ocrelizumab Biomarker Outcome Evaluation (OBOE; ML29966) trial: https://clinicaltrials.gov/study/NCT02688985.
OBJECTIVE: To track changes in N-acetylaspartate and myo-inositol in relapsing MS (RMS) and primary progressive MS (PPMS) patients treated with ocrelizumab over 2 years.
METHODS: Single-voxel MRS at 3T was acquired at baseline in 10 healthy controls (HCs), and weeks 0, 12, 24, 52, and 96 in MS participants at a single center.
RESULTS: Baseline myo-inositol was higher in PPMS than RMS (p = 0.047) and HC (p = 0.001), and correlated with disability across both MS groups (r = 0.57, p = 0.0006). Following treatment with ocrelizumab, both RMS and PPMS demonstrated declines in myo-inositol over time, returning toward HC levels (RMS p = 0.016; PPMS p = 0.004). Conversely, N-acetylaspartate was not different between groups and remained stable over time.
CONCLUSION: Ocrelizumab treatment is associated with declining myo-inositol levels measured by MRS in both RMS and PPMS. Myo-inositol offers a unique biomarker to track resolution of gliosis and reactive microglia with treatment. Furthermore, the relationship between a higher concentration of myo-inositol and greater disability across both MS subtypes at baseline supports the presence of "smouldering inflammation" as a disease process across the spectrum of MS.
CLINICAL TRIAL: Sub-study of the Ocrelizumab Biomarker Outcome Evaluation (OBOE; ML29966) trial: https://clinicaltrials.gov/study/NCT02688985.