Tryptophan pathway profiling in multiple sclerosis patients treated with ocrelizumab

Carolina Ricci¹Matteo Pivetta¹Eleonora Martinis¹Viviana Valeri¹Carolina Colliva²Nicola Giacchè²Simone Lorenzut³Daniela Cargnelutti³Barbara Frossi¹Silvia Tonon^1*

• ¹Department of Medicine, University of Udine, Udine, Italy
• ²TES Pharma S.r.l., Perugia, Umbria, Italy
• ³Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), SOC Neurologia, Dipartimento Testa collo e neuroscienze, Udine, Italy

Significant alterations in L-Tryptophan (Trp) metabolism have been identified among several chronic inflammatory pathologies, including multiple sclerosis (MS). There are three metabolic routes responsible for Trp processing, each capable of producing metabolites that can influence immune and neuronal response: the Kynurenine, Serotonin and Indole pathways. The impact of the host microbiota on these metabolic processes is a multifaceted aspect of MS pathogenesis, with direct and indirect effects being observed. The microbiota is directly responsible for Indole-metabolites production but can also influence Serotonin and Kynurenine pathway by regulating Trp availability or by influencing the enzymatic activity of host-cells. It is noteworthy that commensal microbiota can also be influenced by several MS treatments, which indirectly can influence also Trp metabolism. In this study, we employed mass spectrometry to investigate Trp metabolomics profile in plasma samples collected from healthy controls and Relapsing Remitting MS patients, before and six months after ocrelizumab (OCR) treatment, to verify which metabolites are dysregulated in MS patients and if their alteration is reverted after treatment. The results of our study established concurrent alterations of Trp-related pathways among OCR treated and untreated MS patients, but also a reversion of some metabolites towards a healthy state after treatment. The data presented here could provide a basis for the study of new pathogenetic mechanisms in MS.