A phase 1-2 clinical trial evaluated adeno-associated virus serotype 9 (AAV9) gene therapy delivering functional copies of the GLB1 gene to children with type II GM1 gangliosidosis, a fatal lysosomal storage disorder. The therapy targets the deficient β-galactosidase enzyme that causes toxic ganglioside accumulation in neurons, leading to progressive neurodegeneration and death typically by age 10. This represents a significant advance in treating rare genetic neurological diseases through direct CNS gene delivery. The AAV9 vector's ability to cross the blood-brain barrier makes it particularly suited for neurological applications, building on successful trials in other lysosomal disorders like Tay-Sachs disease. For families facing these devastating diagnoses, gene therapy offers the first potential treatment beyond palliative care. However, the therapy's durability remains uncertain since AAV vectors don't integrate into the genome and may require repeated dosing. The small patient population in rare disease trials also limits statistical power for efficacy assessment. Success here could accelerate development for related gangliosidoses and establish AAV9 as a platform for treating genetic brain disorders, though long-term safety data spanning years will be crucial for broader clinical adoption.