Tryptophan pathway profiling in multiple sclerosis patients treated with ocrelizumab

Area of Science:

• Neuroimmunology
• Metabolomics
• Microbiome-Host Interactions

Background:

• L-Tryptophan (Trp) metabolism is dysregulated in chronic inflammatory diseases like Multiple Sclerosis (MS).
• Trp is processed via Kynurenine, Serotonin, and Indole pathways, significantly influenced by gut microbiota.
• Previous studies have not simultaneously analyzed all three Trp metabolic routes in MS patients before and after Ocrelizumab (OCR) treatment.

Purpose of the Study:

• To comparatively investigate the L-Tryptophan metabolomics profile in MS patients before and after Ocrelizumab (OCR) treatment.
• To explore alterations in Kynurenine, Serotonin, and Indole pathways in MS.
• To assess the impact of OCR treatment on Trp metabolism in MS.

Main Methods:

• Plasma samples from healthy controls and MS patients (pre- and post-OCR treatment) were analyzed using mass spectrometry.
• A comparative metabolomics approach was employed to profile Trp metabolites.

Main Results:

• Concurrent alterations in Trp-related pathways were observed in both treated and untreated MS patients.
• MS patients treated with OCR showed a metabolic profile that partially resembled the healthy state across various pathways.
• The study identified specific metabolite changes related to MS and OCR therapy.

Conclusions:

• L-Tryptophan metabolism is significantly altered in Multiple Sclerosis.
• Ocrelizumab treatment may partially normalize Trp metabolic pathways in MS patients.
• These findings offer new insights into MS pathogenesis and treatment response.