Publication Type Academic Article
Authors Niethammer M, Tang C, Vo A, Nguyen N, Spetsieris P, Dhawan V, Ma Y, Small M, Feigin A, During M, Kaplitt M, Eidelberg D
Journal Sci Transl Med
Volume 10
Issue 469
Date Published 11/28/2018
ISSN 1946-6242
Keywords Brain, Genetic Therapy, Nerve Net, Parkinson Disease
Abstract 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 (GAD) 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 GAD gene therapy developed a unique treatment-dependent polysynaptic brain circuit that we termed as the GAD-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.
DOI 10.1126/scitranslmed.aau0713
PubMed ID 30487248
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