Gene therapy reduces Parkinson's disease symptoms by reorganizing functional brain connectivity.

TitleGene therapy reduces Parkinson's disease symptoms by reorganizing functional brain connectivity.
Publication TypeJournal Article
Year of Publication2018
AuthorsNiethammer M, Tang CC, Vo A, Nguyen N, Spetsieris P, Dhawan V, Ma Y, Small M, Feigin A, During MJ, Kaplitt MG, Eidelberg D
JournalSci Transl Med
Date Published2018 11 28
KeywordsBrain, Dependovirus, Disease Progression, Female, Genetic Therapy, Glutamate Decarboxylase, Humans, Male, Metabolic Networks and Pathways, Middle Aged, Nerve Net, Parkinson Disease, Subthalamic Nucleus, Treatment Outcome

Gene therapy is emerging as a promising approach for treating neurological disorders, including Parkinson's disease (PD). A phase 2 clinical trial showed that delivering glutamic acid decarboxylase () into the subthalamic nucleus (STN) of patients with PD had therapeutic effects. To determine the mechanism underlying this response, we analyzed metabolic imaging data from patients who received gene therapy and those randomized to sham surgery, all of whom had been scanned preoperatively and at 6 and 12 months after surgery. Those who received gene therapy developed a unique treatment-dependent polysynaptic brain circuit that we termed as the -related pattern (GADRP), which reflected the formation of new polysynaptic functional pathways linking the STN to motor cortical regions. Patients in both the treatment group and the sham group expressed the previously reported placebo network (the sham surgery-related pattern or SSRP) when blinded to the treatment received. However, only the appearance of the GADRP correlated with clinical improvement in the gene therapy-treated subjects. Treatment-induced brain circuits can thus be useful in clinical trials for isolating true treatment responses and providing insight into their underlying biological mechanisms.

Alternate JournalSci Transl Med
PubMed ID30487248