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VITAE PHARMACEUTICALS, INC filed this Form S-1 on 08/12/2014
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VTP-43742 in Mouse EAE Model

IL-17 Gene Expression




Figure 11: Left: VTP-43742 treatment ameliorates severity of disease in the EAE model, where mpk refers to mg/kg. Right: VTP-43742 inhibits IL-17 gene expression within inflammatory cells in the spinal cord of treated animals.

        EAE is characterized by an immune mediated inflammatory response in the spinal cord of diseased mice which leads to the loss of the myelin sheaths around the nerve axons in the spinal cord. We therefore examined the effect of VTP-43742 on the spinal cord and the loss of myelin sheaths in EAE animals. Representative histological sections of hematoxylin and eosin, two tissue stains frequently used in the microscopic analysis of tissues, stained spinal cords from animals treated with dosing solution without drug, or vehicle, or VTP-43742 treated animals were examined after disease induction. As shown in Figure 12 below, the loss of axonal myelin sheaths results in the formation of vacuoles, or small bubbles, in the vehicle treated animals, as shown in a spinal cord cross section in Figure 12 on the left, whereas the vacuoles are substantially decreased or absent in the VTP-43742 treated animals as shown in Figure 12 on the right. In addition, inflammation, characterized by lymphocyte and neutrophil infiltration and necrotic cell debris were both significantly reduced in VTP-43742 treated animals compared with vehicle controls. Collectively, these data demonstrate that VTP-43742 is effective in reducing disease activity in a clinically relevant animal model of human MS via blockade of the immune mediated inflammatory process and an inhibition of RORgt driven gene expression.


Figure 12: VTP-43742 reduces histologic abnormalities, indicative of loss of myelin sheaths around the nerve cell axons, in EAE mice.