The first head-to-head comparison using microglia imaging of two FDA-approved disease-modifying treatments (DMTs) for multiple sclerosis is underway. Watch Center Director Robert Zivadinov, MD, PhD explain a study underway at the Buffalo Neuroimaging Analysis Center (BNAC) on NeurologyLive®.

“What’s of interest to people with MS and clinicians is that both of the DMTs are approved and in use,” said Zivadinov. “And what’s of particular interest to pharmaceutical researchers is that the methodology is unique. This is the first time that four separate imaging methodologies and measures have been used in coordination to determine the evolution of chronic active lesions in MS.”

The study, funded by Novartis Pharmaceuticals, seeks to determine if drugs like siponimod (Mayzent™)—approved to treat relapsing and remitting MS—may inhibit microglia activation more than anti-inflammatory drugs like ocrelizumab (Ocrevus™). Recent studies suggest that siponimod may cross the blood-brain barrier, enter the central nervous system, and bind specifically to the SP1 receptor 5, which is important for microglia activation, for oligodendrocyte activity, and for astrocytes.

The four imaging modalities include: 1) quantitative susceptibility mapping to measure paramagnetic rim lesions; 2) mapping slowly expanding lesions over time using conventional MRI sequences; 3) positron emission tomography (PET) using an extremely sensitive translocator binding benzodiazepine receptor protein called 18F-PBR06 to detect binding in lesions, perilesional tissue, or normal-appearing white and gray matter; 4) use of ferumoxytol (Feraheme™) an FDA-approved drug for treatment of anemia, that can be used as an MRI contrast agent binding to macrophages and resident microglia, which results in visualization of contrast-enhancing lesions, similar in their aspect to the gadolinium contrast-enhancing lesions that are currently used for clinical trials in MS.

The study is probably the most sophisticated attempt to prove whether microglia activation, a marker for relapsing and remitting MS, can be stopped with a high anti-inflammatory B-cell depleter or with a more microglia-oriented S1P inhibitor that is working on S1P receptor 5. The study is expected to be completed in late 2026 with findings published soon thereafter.

Watch the video on NeurologyLive® here.