AAV-GRN partially corrects motor deficits and ALS/FTLD-related pathology in Tmem106b^-/-Grn^-/- mice.

ABSTRACT: Loss of function of progranulin (PGRN), encoded by the granulin (GRN) gene, is implicated in several neurodegenerative diseases. Several therapeutics to boost PGRN levels are currently in clinical trials. However, it is difficult to test the efficacy of PGRN-enhancing drugs in mouse models due to the mild phenotypes of Grn^-/- mice. Recently, mice deficient in both PGRN and TMEM106B were shown to develop severe motor deficits and pathology. Here, we show that intracerebral ventricle injection of PGRN-expressing AAV1/9 viruses partially rescues motor deficits, neuronal loss, glial activation, and lysosomal abnormalities in Tmem106b^-/-Grn^-/- mice. Widespread expression of PGRN is detected in both the brai

SUBMITTER: Feng T 

PROVIDER: S-EPMC10371829 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature