Dimethyl fumarate treatment in relapsing remitting MS changes the inflammatory CSF protein profile by a prominent...

Area of Science:

• Neuroscience
• Immunology
• Proteomics

Background:

• Dimethyl fumarate (DMF) is a widely used treatment for multiple sclerosis (MS).
• The precise mechanisms of action for DMF remain incompletely understood.
• Targeted proteomics can elucidate DMF's effects and identify treatment response biomarkers.

Purpose of the Study:

• To investigate the impact of DMF on inflammation- and neuro-associated proteins in both plasma and cerebrospinal fluid (CSF) of MS patients.
• To identify potential protein biomarkers for predicting patient response to DMF therapy.

Main Methods:

• Employed proximity extension assay (PEA), a highly sensitive and specific method.
• Measured 182 inflammation- and neuro-associated proteins in paired plasma and CSF samples from 28 and 12 MS patients, respectively, before and after one year of DMF treatment.
• Utilized clinical examination, MRI, statistical analyses, network analysis, and regression models to evaluate disease activity and identify biomarkers.

Main Results:

• Observed a consistent decrease in T-helper 1 (Th1)-associated proteins (e.g., CXCL10, granzyme A) in CSF after one year of DMF treatment, with an increase in IL-7.
• Noted that plasma protein level changes did not mirror those in CSF.
• Identified potential biomarker candidates, including plexins and neurotrophins, using logistic regression for predicting treatment response.

Conclusions:

• DMF therapy demonstrably alters CSF protein profiles, notably reducing Th1-associated pro-inflammatory proteins.
• CSF proteins linked to neurodegeneration show predictive value for treatment response.
• Protein biomarkers show significant potential for advancing personalized medicine approaches in MS treatment.