Researchers reported optimization efforts for AAV9‑based gene therapy targeting SMARD1 (spinal muscular atrophy with respiratory distress 1) and related CMT2S models, detailing adjustments that improve delivery, expression, and safety profiles. The work addresses dosing, vector design, and target tissue transduction to enhance therapeutic windows. The study underscores the iterative engineering required for rare‑disease AAV programs: vector serotype, promoter choice, and manufacturing can change efficacy and immune responses. Those optimizations aim to lower neurotoxicity risks while preserving motor neuron rescue, informing IND‑enabling packages and clinical trial design for motor neuron disorders.