AAV9-mediated βIII-tubulin Ser172 phospho-mimic expression improves arrhythmic and inflammatory remodeling in dystrophic cardiomyopathy

The study builds on earlier work where a Ser172Glu (S172E) phospho-mimic knock-in preserved microtubule organization and reduced cardiac pathology in mdx mice. Here, the authors tested whether this benefit could be achieved via AAV9 gene delivery, a clinically relevant approach. They generated an AAV9 vector expressing βIII-tubulin with the S172E mutation and evaluated its effects in mdx mice, focusing on connexin-43 regulation, inflammatory markers, and arrhythmia susceptibility. Results reportedly show improved microtubule stability, reduced Cx43 dysregulation, and attenuated arrhythmic and inflammatory remodeling. These findings support further development of AAV9-mediated tubulin modification as a potential therapy for DMD cardiomyopathy, though additional safety and efficacy studies in larger models are needed.