Liver injury in cynomolgus monkeys following intravenous and intrathecal scAAV9 gene therapy delivery.

ABSTRACT: Hepatotoxicity associated with intravenous/intrathecal adeno-associated virus (AAV) gene therapy has been observed in preclinical species and patients. In nonhuman primates, hepatotoxicity following self-complementary AAV9 administration varies from asymptomatic transaminase elevation with minimal to mild microscopic changes to symptomatic elevations of liver function and thromboinflammatory markers with microscopic changes consistent with marked hepatocellular necrosis and deteriorating clinical condition. These transient acute liver injury marker elevations occur from 3-4 days post intravenous administration to ∼2 weeks post intrathecal administration. No transaminase elevation or microscopic changes were observed with intrathecal administration of empty capsids or a "promoterless genome

SUBMITTER: Hudry E 

PROVIDER: S-EPMC10556189 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature