Adeno-associated viral vector serotype 9–based gene therapy for Niemann-Pick disease type A

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Science Translational Medicine  21 Aug 2019:
Vol. 11, Issue 506, eaat3738
DOI: 10.1126/scitranslmed.aat3738

Safe and effective gene delivery

Niemann-Pick type A disease (NPD-A) is caused by loss-of-function mutations in the gene encoding for acid sphingomyelinase (ASM). Patients present mental retardation with prominent loss of early motor skills and cognitive decline and early death. Gene replacement therapy has been shown to be effective in other monogenic neurological disorders. Now, Samaranch et al. evaluated the safety and efficacy of adeno-associated viral vector serotype 9 (AAV9)–based gene therapy. AAV9-mediated delivery of human ASM in the cerebellomedullary cistern allowed widespread gene expression in the brain and spinal cord of nonhuman primates without signs of toxicity. The treatment prevented motor and memory impairment and increased survival in a mouse model of NPD-A.

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