21 August 2019
Vol 11, Issue 506

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ONLINE COVER Widespread Benefits. Patients with Niemann-Pick disease type A (NPD-A) develop multi-organ pathologies. Within the brain, NPD-A triggers neurodegeneration in several regions, including the cerebellum (depicted here). NPD-A is caused by loss-of-function mutations in the gene encoding acid sphingomyelinase (ASM). Because prior research has shown that intracerebral gene therapy using adeno-associated viral vector (AAV) is not distributed beyond the area surrounding the injection site, Samaranch et al. delivered AAV-ASM through the cerebellomedullary cistern (CM). CM injection of AAV9-ASM in nonhuman primates resulted in widespread gene distribution throughout the nervous system, without signs of toxicity. In a mouse model of NPD-A, treatment ameliorated liver pathology and reduced neurodegeneration in several brain areas. [CREDIT: SAMARANCH ET AL./SCIENCE TRANSLATIONAL MEDICINE]