Circulating extracellular vesicles as biomarkers to monitor response to Multiple Sclerosis therapy.

ABSTRACT: In the last two decades, several disease-modifying treatments (DMTs) have been developed for MS. These therapies are based on the modulation of the immune system and the aim to reduce the disease activity. However, as the natural course of the disease is unpredictable, the benefit of each treatment in each individual patient is still unknown and clinical decisions are very complicated. Some patients initiate treatment but continue with relapses, new lesions in the central nervous system, or show worsening disability. When this occurs, the response of the treatment is considered suboptimal and has to be switched to a more effective treatment, albeit generally with a higher risk of serious adverse effects. Currently, these decisions are made on a case-by-case basis when the lesions in the CNS and the increase in disability have occurred. This is likely due to multiple factors, including the absence of highly predictive, widely used treatment response biomarkers with reasonable sensitivity and specificity that step over the disease heterogeneity and that can be applied in real-life clinical practice. As a result, a high percentage of MS patients do not present adequate control of their disease activity while receiving DMT. In this context, a biomarker that anticipates treatment response or predicts treatment failure would help to make the change before irreversible injury occurs. We aim to analyse whether proteins and miRNAs derived from patients' circulating EVs could provide relevant information about the patient's response to treatment. To build on this, we assessed EV levels, size, microRNA, and protein content from neurons, oligodendrocytes, B and T lymphocytes, pre- and 3 months post-treatment initiation, and correlated with therapeutic response over 12 months in MS patients. Treatment response treatment was evaluated using ‘no evidence of disease activity’ (NEDA5) composite that includes the following clinical parameters: clinical relapses, new lesions on MRI, motor and cognitive disability progression and brain atrophy.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Extracellular Vesicle, Blood

SUBMITTER: Susana Bravo  

LAB HEAD: Susana Bravo

PROVIDER: PXD048002 | Pride | 2025-05-06

REPOSITORIES: Pride