Natalizumab in progressive MS: results of an open-label, phase 2A, proof-of-concept trial

Area of Science:

• Neuroimmunology
• Clinical Neurology
• Biomarker Research

Background:

• Natalizumab, an immune-modulating therapy, is known to inhibit immune cell migration to the central nervous system (CNS).
• Its potential benefit in progressive forms of multiple sclerosis (MS) warrants investigation.

Purpose of the Study:

• To evaluate the efficacy of natalizumab in patients with progressive multiple sclerosis (MS).
• To assess the impact of natalizumab on biomarkers of inflammation and tissue damage within the cerebrospinal fluid (CSF) and CNS.

Main Methods:

• An open-label, Phase 2A study involving 24 patients with progressive MS treated with natalizumab for 60 weeks.
• Assessment of treatment response using cerebrospinal fluid (CSF) analysis and magnetic resonance imaging (MRI).
• Primary endpoint: change in CSF osteopontin, a marker of intrathecal inflammation, from baseline to week 60.

Main Results:

• Seventeen patients completed the 60-week study without new safety concerns.
• Significant reduction in CSF osteopontin levels by 65 ng/mL (p = 0.0004), indicating decreased intrathecal inflammation.
• Observed reductions in other CSF biomarkers of inflammation, axonal damage, and demyelination.
• Increased magnetization transfer ratio in cortical gray and white matter, correlating with reduced CSF neurofilament light chain.

Conclusions:

• Natalizumab treatment demonstrably reduces intrathecal inflammation and tissue damage in progressive MS.
• Findings suggest that systemic inflammation plays a role in the pathogenesis of progressive MS.
• The study validates the use of CSF biomarkers in proof-of-concept trials, enabling smaller sample sizes and shorter study durations.