Figure 8. Long term in vivo safety study in WT mice at 28 days or 365 days following treatment at P42 highlighted no adverse events or histopathology were present.

Various vector promoter sequences were tested including the our treatment vector (CBh-hAP4B1). (A) Serum chemistry, including: white blood cell, lymphocyte and monocyte counts were analysed at 28 days post treatment (DPT) and 1 year post treatment. (B) Histopathological assessments of WT mouse livers at 1 year following treatment with hAP4B1 vectors showed no adverse effects on inflammation, necrosis, steatosis or fibrosis compared to untreated the cohort. No adverse effects were observed in heart, brain and spinal cord (see Appendix Table S1 for data set). (C) RT-qPCR of total RNA extracted from mice at 28 DPT demonstrated that the CBh promoter gave consistently higher levels of hAP4B1 mRNA expression across the CNS compared to the SYN promoter. Data shows high hAP4B1 mRNA expression within the liver and heart, which indicates CSF leakage in this study. Data are presented as mean ± SEM, 28-day sacrifice n = 6 per group (3 males and 3 females); 1-year sacrifice n = 6 per group (3 males and 3 females) and were analysed via a one-way ANOVA with Tukey’s multiple comparisons test. Stars indicate p ≤ 0.01 (**), ns = not significant, WBC: p = 0.0014, Lymphocyte: p = 0.0028. Source data are available online for this figure.