Dopaminergic restoration of prefrontal cortico-putaminal network in gene therapy for aromatic l-amino acid decarboxylase deficiency.

ABSTRACT: Aromatic l-amino acid decarboxylase (AADC) is an essential dopamine-synthesizing enzyme. In children with AADC deficiency, the gene delivery of AADC into the putamen, which functionally interacts with cortical regions, was found to improve motor function and ameliorate dystonia. However, how the restoration of dopamine in the putamen in association with cortico-putaminal networks leads to therapeutic effects remains unclear. Here, we examined neuroimaging data of eight patients with AADC deficiency (five males and three females, age range 4-19 years) who received the AADC gene therapy of the bilateral putamen in an open-label phase 1/2 study. Using high-resolution positron emission tomography with a specific AADC tracer, 6-[¹⁸F]fluoro-l-m-tyrosine (FMT), we showed that FM

SUBMITTER: Onuki Y 

PROVIDER: S-EPMC8374966 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature