An open-label phase 1–2 study tested a single intravenous administration of a β-galactosidase-encoded AAV9 vector in the first nine patients with GM1 gangliosidosis type II.[1] The primary endpoint was safety at 3 years; secondary and exploratory outcomes included cerebrospinal fluid (CSF) levels of GM1 ganglioside and β-galactosidase, clinical assessments, and neuroimaging.[1] The only serious vector-induced adverse event was vomiting requiring hospitalization for intravenous hydration.[1] Serum levels of the enzymes aspartate aminotransferase and alanine aminotransferase increased after gene therapy, but returned to pretreatment levels within 18 months.[1] In communication and motor skills, there was stability in expressive communication and gross motor, but a significant decrease in fine motor and receptive communication.[1] Median CGI-Improvement scores at 2 and 3 years were "minimal improvement" or "no change".[1] In the CSF of all participants, β-galactosidase increased and GM1 ganglioside decreased; MRI showed improved myelination and less loss of brain atrophy, MRS reduced NAA loss compared to historical controls.[1] The therapy was generally well tolerated and indicated improvement in biochemical markers and developmental stabilization.[1]