Researchers reported optimized AAV9-based gene therapy strategies for SMARD1 (spinal muscular atrophy with respiratory distress type 1) that improve delivery and therapeutic indices in preclinical testing. The work focuses on vector design, dosing, and safety profiling to enhance motor neuron rescue while limiting systemic toxicity. The study assessed AAV9 tropism, expression levels, and functional outcomes in disease models relevant to SMARD1 and related peripheral neuropathies such as CMT2S. Authors report improved respiratory and motor endpoints with modified constructs and administration protocols. These optimizations are positioned as critical steps toward clinical translation for rare motor neuron disorders, providing a template for regulators and sponsors weighing AAV9 trials in pediatric neuromuscular diseases.