CSF inflammation and axonal damage are increased and correlate in progressive multiple sclerosis

Area of Science:

• Neuroimmunology
• Biomarker Discovery

Background:

• The mechanisms driving progressive multiple sclerosis (MS) remain unclear.
• Pathological studies link widespread brain inflammation in progressive MS to disease progression and axonal damage.

Purpose of the Study:

• To investigate cerebrospinal fluid (CSF) biomarkers in progressive MS.
• To determine the association between inflammation and axonal damage in progressive MS.

Main Methods:

• CSF samples analyzed using ELISA from patients with secondary progressive MS (SPMS), primary progressive MS (PPMS), relapsing-remitting MS (RRMS), and non-inflammatory neurological disease (NIND).
• Follow-up CSF analysis after one year for SPMS patients in an MBP8298 peptide clinical trial.

Main Results:

• Inflammatory biomarkers (osteopontin, MMP9, CXCL13) and biomarkers of axonal damage (NFL) and demyelination (MBP) were elevated in MS patients compared to NIND.
• In progressive MS, CSF osteopontin and CXCL13 correlated with NFL; osteopontin and MMP9 correlated with MBP.
• MBP8298 treatment did not alter biomarker levels after one year; most biomarkers remained elevated, except MBP.

Conclusions:

• CSF biomarkers for inflammation, axonal damage, and demyelination are persistently elevated and interconnected in progressive MS.
• Findings support a relationship between inflammation, axonal damage, and demyelination, mirroring pathology studies.
• CSF biomarkers are valuable tools for progressive MS clinical trials.