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. 2023 Nov 2;31:101149. doi: 10.1016/j.omtm.2023.101149

Figure 7.

Figure 7

Mechanisms of brain correction after gene therapy

(A) Quantification of IDS-positive cells in brains of gene therapy-treated mice and untreated Idsy/− and WT mice. (B) Example of distribution of IDS-positive cells in a IDSco-treated mouse. Examples of other treatment conditions are shown in Figure S7. (C) IDS staining in sagittal sections of cortex, brainstem, choroid plexus, and meninges. Representative pictures of other treatment conditions are shown in Figure S6. Scale bar, 25 μm. (D) Quantification of GFP-positive cells in brain of GFP-treated Idsy/− mice and WT. Representative pictures are shown in Figure S6. (E) VCN per genome measured in brain by qPCR on PSI and Albumin loci. (F) Chimerism analysis of brain measured by allele-specific qPCR on the Cd45.1 locus. Validation data are shown in Figure S10. (G) Non-linear regression analysis between VCN in brain and cerebral heparan sulfate. (H) Non-linear regression analysis between chimerism in brain and heparan sulfate in brain. (I) Functional ELISA analysis of IDS, IDS.ApoE2, and IDS.RAP12x2 proteins using the LRP-1 receptor (cluster IV). (J) IDS and IDS.IGF2 proteins binding to the CI-M6P/IGF2 receptor (domain 11) in a functional ELISA. (K) Non-linear regression analysis between brain heparan sulfate content and IDS enzyme activity in plasma. Data are presented as means ± SEM. In (E) and (F) data were analyzed by one-way ANOVA with Bonferroni’s correction. Regression analysis of (G), (H), and (K) is shown in Table S1. Asterisks represent significance vs. WT; hashs represent significance vs. Idsy/−. In (E) ˆ represent significance vs. the IDS.IGF2co MOI 3 group. Other significant comparisons are indicated by brackets. PV, perivascular cells; PC, parenchymal cell; Mg, meninges; CP, choroid plexus. (A–C) n = 3. (E and F) Experiment 1: n = 5 or 6 per group. Experiment 2: IDSco, IDS.IGF2co, GFP, Idsy/− and WT n = 6; IDS.ApoE2co n = 10; IDS.RAP12x2co n = 7. (G and H) n = 6. (I and J) n = 3. ∗p ≤ 0.05. #p ≤ 0.05. ˆp ≤ 0.05, ˆˆp ≤ 0.01, ˆˆˆp ≤ 0.001, ˆˆˆˆp ≤ 0.0001.