Fig. 4: An early and single dose of AAV9:PKP2 significantly reduced arrhythmias, improved cardiac function, and prolonged median lifespan to ≥ 58 weeks post AAV administration. | Communications Medicine

Fig. 4: An early and single dose of AAV9:PKP2 significantly reduced arrhythmias, improved cardiac function, and prolonged median lifespan to ≥ 58 weeks post AAV administration.

From: AAV9:PKP2 improves heart function and survival in a Pkp2-deficient mouse model of arrhythmogenic right ventricular cardiomyopathy

Fig. 4: An early and single dose of AAV9:PKP2 significantly reduced arrhythmias, improved cardiac function, and prolonged median lifespan to ≥ 58 weeks post AAV administration.

a Study design to evaluate TN-401 or AAV9:mPkp2 efficacy using Pkp2-cKO ARVC mouse model. AAV9 was injected three weeks before gene deletion, TN-401 at 3E13 vector genomes per kilogram bodyweight (vg/kg) and AAV9:mPkp2 at 5E13 vg/kg. Echocardiograph (Echo) and electrocardiogram (EKG) data were collected at week 3 and week 4 post gene deletion. b Raw EKG traces showed a significant contrast in spontaneous arrhythmias in Pkp2-cKO mice in the absence and the presence of TN-401 or AAV9:mPkp2 treatment. PVCs, premature ventricular contractions; NSVT, non-sustained ventricular tachycardia. The right graph summarized arrhythmia scores representing frequency and severity of ventricular arrhythmias. This arrhythmia score is an overall composite score estimating arrhythmia burden (see Supplementary Table 1). Statistical significance in response to TN-401 or AAV9:mPkp2 treatment was evaluated using nonparametric Kruskal-Wallis test with Dunn’s correction. c TN-401 or AAV9:mPkp2 treatment of Pkp2-cKO mice showed efficacy in reducing RV dilation as estimated by RV area normalized to body weight (mm2/g) and (d) maintaining left ventricular ejection fraction at 4 weeks post gene deletion. Time course of RV dilation was evaluated with ordinary Two-Way ANOVA (Tukey’s post-hoc test), statistical significance shown between the vehicle treated cKO animals and TN-401 treated cKO animals. EF% was evaluated with ordinary One-Way ANOVA (Tukey’s post-hoc test). e Kaplan-Meier survival curve showed that TN-401 extended median lifespan of Pkp2-cKO mice by ≥58 weeks post gene deletion. Numbers in paratheses showed dead vs live animals by the time of takedown. Animals treated by AAV9:mPkp2 (in green line) were taken down early for exploratory studies. Quantified data were presented as mean ± s.e.m. Sample size n = 9, 10, 11, 10 for WT, cKO, cKO+TN-401, and cKO+AAV9:mPkp2, respectively.

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