Journal: Molecular Therapy. Nucleic Acids

Article Title: Preclinical evaluation of stereopure antisense oligonucleotides for allele-selective lowering of mutant HTT

doi: 10.1016/j.omtn.2024.102246

Figure Lengend Snippet: SNP3-targeting oligonucleotides dose-dependently decrease mHTT in cortex and striatum of BACHD mice Dosing regimen for administration of PBS or oligonucleotide (12.5 μg, 25 μg, 50 μg, or 100 μg) to BACHD mice and sample collection 15 days after first dose is shown (A). The relative fold change of human mHTT to mouse Tubb3 as a percentage of PBS in the cortex (B) and striatum (C) is shown at 2 weeks after the first administration ( n = 7–8 per treatment). Data shown as mean ± SD (∗ p ≤ 0.05, ∗∗ p ≤ 0.01, ∗∗∗ p ≤ 0.001, ∗∗∗∗ p ≤ 0.0001 vs. PBS). p values were calculated via one-way ANOVA followed by two-tailed post-hoc comparisons to PBS assuming equal variance. Dosing regimen for administration and sample collection 29 days after first dose is shown in (D). The relative fold change of human mHTT to mouse Tubb3 as a percentage of PBS in the cortex (E) and striatum (F) is shown at 4 weeks after the first administration (n = 7–8 per treatment). Data shown as mean ± SD (∗ p ≤ 0.05, ∗∗ p ≤ 0.01,∗∗∗ p ≤ 0.001, ∗∗∗∗ p ≤ 0.0001 vs. PBS). p values were calculated via one-way ANOVA followed by two-tailed post hoc comparisons to PBS assuming equal variance.

Article Snippet: The transgenic lines BACHD (bacterial artificial chromosome-mediated transgenic Huntington’s disease, Jackson Laboratory Cat. No. 008197) and Hu97/18 used for in vivo studies have been described previously., Male and female mice were 8–12 weeks of age at the time of dosing.

Techniques: Two Tailed Test

Journal: Molecular Therapy. Nucleic Acids

Article Title: Preclinical evaluation of stereopure antisense oligonucleotides for allele-selective lowering of mutant HTT

doi: 10.1016/j.omtn.2024.102246

Figure Lengend Snippet: SNP3-targeting oligonucleotides durably reduce mHTT in the cortex and striatum of BACHD mice Dosing regimens and time of sample collection post-first dose for studies 1 and 2 are shown (A). Oligonucleotides or PBS were administered by ICV injection (3 × 100 μg). For study 1, the relative fold change of human mHTT to mouse Tubb3 as a percentage of PBS in the cortex (B) and striatum (C) is shown at 2, 4, 8, and 12 weeks after the first administration ( n = 7–8 per treatment). For study 2, the relative fold change of human mHTT to mouse Tubb3 as a percentage of PBS in the cortex (D) and striatum (E) is shown at 2, 4, and 12 weeks after the first administration ( n = 8 per treatment). For (B)–(E), data are shown as mean ± SD (∗ p ≤ 0.05; ∗∗ p ≤ 0.01; ∗∗∗ p ≤ 0.001; ∗∗∗∗ p ≤ 0.0001 compared with PBS). p values were calculated via two-way ANOVA (B–D), or White-adjusted two-way ANOVA (E) followed by two-tailed post-hoc comparisons to PBS per week with equal (B–D) or unequal (E) variance.

Article Snippet: The transgenic lines BACHD (bacterial artificial chromosome-mediated transgenic Huntington’s disease, Jackson Laboratory Cat. No. 008197) and Hu97/18 used for in vivo studies have been described previously., Male and female mice were 8–12 weeks of age at the time of dosing.

Techniques: Injection, Two Tailed Test

Journal: Molecular Therapy. Nucleic Acids

Article Title: Preclinical evaluation of stereopure antisense oligonucleotides for allele-selective lowering of mutant HTT

doi: 10.1016/j.omtn.2024.102246

Figure Lengend Snippet: SNP3-targeting oligonucleotide PK/PD parameters based on cortical and striatal tissue of BACHD mice

Article Snippet: The transgenic lines BACHD (bacterial artificial chromosome-mediated transgenic Huntington’s disease, Jackson Laboratory Cat. No. 008197) and Hu97/18 used for in vivo studies have been described previously., Male and female mice were 8–12 weeks of age at the time of dosing.

Techniques:

Journal: Neurobiology of disease

Article Title: Mural cell dysfunction leads to altered cerebrovascular tau uptake following repetitive head trauma

doi: 10.1016/j.nbd.2020.105237

Figure Lengend Snippet: Timeline of the brain injury paradigm and tissue collection for the mouse studies. Human tau (hTau) mice at 3 months of age received 2 injuries per week for 3 months. As a control, sham animals did not receive any brain injuries, but were exposed to anesthesia for the same length of time as the injured mice and under the same paradigm (2 exposures per week for 3 months). Mice were euthanatized and tissue was collected at 24 h, 3 months, 6 months, and 12 months after the final brain injury or anesthesia exposure (blue boxes). Moreover, transgenic mural cell-depleted animals, PDGFRβ(+/−) (green box), and a mouse model of Alzheimer’s disease, PSAPP (red box), were euthanatized and tissue collected at 12 months and 18 months of age, respectively. Of note, neither the PDGFRβ(+/−) nor PSAPP animals were administered any brain injuries. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Article Snippet: Human tau (hTau) mice (cat#005491) were purchased from the Jackson Laboratory (Bar Harbor, ME, USA).

Techniques: Control, Transgenic Assay