INVESTIGATION OF THE PROTECTIVE AND THERAPEUTIC EFFECTS OF FILAMIN-A INHIBITORS IN A MOUSE MODEL OF MULTIPLE SCLEROSIS

To investigate the protective and therapeutic effects of the Filamin-A (FLNA) inhibitor Simuflam (PTI-125) in an experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis (MS), a disorder characterized by inflammation, demyelination, and neurodegeneration. Since current disease-modifying therapies are insufficient to prevent progressive neuronal damage, FLNA represents a promising novel target.
Forty-two male C57BL/6 mice were assigned to naïve and EAE groups, each subdivided into Simuflam-treated and untreated controls. EAE was induced using MOG35–55 peptide. Simuflam (10 mg/kg) was administered intraperitoneally in prophylactic and therapeutic regimens. Daily clinical scoring was performed. At the study endpoint, spleen, lymph node, and central nervous system tissues were collected for flow-cytometric analysis of CD4⁺, CD8⁺, and FOXP3⁺ T-cell subsets, as well as cytokine profiling (IL-2, IL-17A, IL-22, IFN-γ, TNF-α, and GM-CSF). Statistical significance was set at p < 0.05.
Simuflam modestly reduced clinical disease progression in EAE mice, although the change was not statistically significant. In naïve mice, Simuflam reduced CD4⁺ T-cell frequency and significantly increased IL-17A levels. In EAE mice, Simuflam increased splenic CD4⁺ and CD8⁺ T-cell ratios but decreased these subsets in lymph nodes. FOXP3⁺ regulatory T-cell frequencies demonstrated tissue-specific variation. Cytokine analyses showed elevations in IL-2, IL-22, and GM-CSF in treated groups.
Simuflam-mediated FLNA inhibition produced measurable immunomodulatory effects in the EAE model. These findings suggest that FLNA may serve as a potential therapeutic target in MS, warranting additional mechanistic and translational research.
Keywords: Filamin-A, Simuflam, multiple sclerosis, EAE, T cells.