A research team demonstrated a novel gene therapy using adeno-associated virus (AAV) to deliver RNA interference targeting the ataxin-2 gene, significantly extending survival and mitigating pathology in a TDP-43 mouse model. TDP-43 proteinopathy underlies diseases such as ALS and frontotemporal dementia, but direct treatments have been elusive due to the protein's essential cellular roles. By partially reducing ataxin-2 expression, a genetic modifier of TDP-43 toxicity, the approach offers a promising strategy to indirectly alleviate neurodegeneration. The use of a neurotropic AAV vector ensures targeted, sustained gene silencing in relevant neuronal populations.