Twenty-six TMEV injected mice were treated at 1-month post induction (mPI) with iBTK (n=13) or vehicle control (n= 13). Clinical disability, weight and rotarod performance was recorded at 1, 2, 3, and 5 mPI. Histology analysis was performed on spinal cord and brain tissue at 3 and 5 mPI with Iba1 staining. ELISA was conducted to confirm TMEV infection. CD19 expressing B-cell fraction of peripheral blood mono-nuclear cells was quantified.

ELISA confirmed anti-TMEV antibodies in infected animals. CD19 expressing B-cell fraction was significantly reduced in iBTK (6.65±1.92%) relative to vehicle treated mice (12.51± 2.34%) (p=0.043). IBTK significantly improved longitudinal changes in CDS (p<0.001), body weights (p=0.033) and rotarod latency measures (p=0.0477) in iBTK TMEV mice. Additionally, at 3 mPI TMEV, animal spinal cord lesion area was significantly lower in white matter (WM) regions (p=0.016) and was trending lower in grey matter regions (p=0.107) in iBTK relative to vehicle treated mice. The WM lesion area remained lower in iBTK treated mice at 5 mPI (p=0.027). Analysis of cerebellum and spinal tissue at 3 mPI found that vehicle treated mouse presented with higher density of proliferation nuclear antigen positive cells.

Treatment with iBTK decreased B-cell fraction and microglia activation in TMEV mice, resulting in lower lesion burden and reduced clinical disability, body weight loss and motor dysfunction. Ongoing studies will assess the effect of iBTK on neuroimaging measures of immune cell infiltration and the presence of neurodegeneration in the CNS.