Blood Chemistry Analysis in an Active Pneumocystis Pneumonia (PCP) Model Treated with Selective CARD9 Inhibitor BRD5529

ABSTRACT Background Pneumocystis pneumonia (PCP) in AIDS and other immunosuppressive states that result from absence of CD4 lymphocytic immunity, continues to be a significant cause of morbidity and mortality. We and others have shown the importance of CARD9 in PCP and other fungal infections, respectively. BRD5529 has been shown to be an effective in vitro and in vivo (18 hour) inhibitor of Pneumocystis β-glucans induced proinflammatory response. These recent results, along with recent general safety and toxicology assessments suggests the application of BRD5529 in an active PCP mouse model of infection to assess initial blood toxicology parameters. Methods To assess preliminary blood toxicology, mice were injected intraperitoneally (IP) daily either with vehicle or BRD5529 at 1.0 mg/kg for one week starting at the 6th week of the PCP mouse model. After one week, mice were sacrificed, and blood collection postmortem was performed for blood chemistry analysis. Results Analysis of blood chemistry showed a significant reduction in blood urea nitrogen (BUN) in the BRD5529 IP treated PCP mice cohort compared to the vehicle control group. All other blood chemistry parameters were not significantly different between the two groups. Conclusions BRD5529 in this preliminary PCP treatment model displayed only significant changes in BUN levels in the BRD5529 treatment group versus the vehicle control group. All other blood chemistry parameters were statistically similar between the two groups.