Focal lesions following intracerebral gene therapy for mucopolysaccharidosis IIIA.

ABSTRACT:

Objective

Mucopolysaccharidosis type IIIA (MPSIIIA) caused by recessive SGSH variants results in sulfamidase deficiency, leading to neurocognitive decline and death. No disease-modifying therapy is available. The AAVance gene therapy trial investigates AAVrh.10 overexpressing human sulfamidase (LYS-SAF302) delivered by intracerebral injection in children with MPSIIIA. Post-treatment MRI monitoring revealed lesions around injection sites. Investigations were initiated in one patient to determine the cause.

Methods

Clinical and MRI details were reviewed. Stereotactic needle biopsies of a lesion were performed; blood and CSF were sampled. All samples were used for viral studies. Immunohistochemistry, electron microscopy, and transcriptome analysis were performed on brain tissue

SUBMITTER: Bugiani M 

PROVIDER: S-EPMC10270249 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature