Novel biomarkers and interferon signature in secondary progressive multiple sclerosis

Avital Fogel1, Maya Olcer1, Aika Goel1

  • 1Department of Neurology, University of Chicago, Chicago, IL 60637, USA.

PubMed

Insights

Multiple sclerosis (MS) involves immune dysregulation. Gene expression analysis reveals distinct patterns in Relapsing-Remitting MS and Secondary Progressive MS, offering potential therapeutic targets for neurodegeneration and immune control.

Area of Science:

  • Neuroimmunology
  • Genomics
  • Neurodegenerative Diseases

Background:

  • Multiple sclerosis (MS) is characterized by immune dysregulation and impaired interferon-beta (IFN-β) signaling.
  • Secondary Progressive MS (SPMS) presents with progressive neurodegeneration and reduced treatment efficacy.
  • Relapsing-Remitting MS (RRMS) and SPMS show distinct molecular profiles compared to healthy individuals.

Purpose of the Study:

  • To investigate gene expression differences in RRMS and SPMS.
  • To identify potential biomarkers for immune regulation and neurodegeneration in MS.
  • To evaluate the effect of IFN-β treatment on gene expression in SPMS.

Main Methods:

  • Differential gene expression analysis comparing RRMS, SPMS, and healthy controls.
  • Analysis of serum protein balance (Th1/Th2).
  • Assessment of gene expression changes following IFN-β treatment in SPMS patients.

Main Results:

  • RRMS exhibited 8700 differentially expressed genes (DEG) compared to controls, while SPMS showed 3900 DEG.
  • SPMS had lower expression of olfactory receptor, WNT/ß-catenin, and metallothionein genes compared to RRMS.
  • IFN-β treatment reduced pro-inflammatory gene expression and increased metallothionein gene expression in SPMS.

Conclusions:

  • Gene expression patterns differentiate MS subtypes and offer insights into disease mechanisms.
  • Olfactory receptor, WNT/ß-catenin, and metallothionein pathways are implicated in MS progression.
  • IFN-β demonstrates potential for modulating immune responses and promoting repair in SPMS through gene expression changes.