Gene Therapy Forms New Polysynaptic Pathways in Parkinson's

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Gene Therapy Forms New Polysynaptic Pathways in Parkinson's
Gene Therapy Forms New Polysynaptic Pathways in Parkinson's

WEDNESDAY, Nov. 28, 2018 (HealthDay News) -- For patients with Parkinson's disease (PD) undergoing gene therapy, new polysynaptic functional pathways develop in the brain, according to a study published in the Nov. 28 issue of Science Translational Medicine.

Martin Niethammer, M.D., Ph.D., from The Feinstein Institute for Medical Research in Manhasset, New York, and colleagues examined the mechanism underlying the therapeutic effects seen in a phase 2 clinical trial involving the delivery of glutamic acid decarboxylase (GAD) into the subthalamic nucleus (STN) of patients with PD. Metabolic imaging data were analyzed from patients who received gene therapy and those randomly assigned to sham surgery. All patients were scanned preoperatively and at six and 12 months postoperatively.

The researchers found that participants who received GAD gene therapy developed a unique treatment-dependent polysynaptic brain circuit, reflecting the formation of new polysynaptic functional pathways linking the STN to motor cortical regions; the circuit was termed the GAD-related pattern (GADRP). When blinded to treatment received, patients in the treatment group and sham group expressed the previously reported placebo network (sham surgery-related pattern). In gene therapy-treated patients, only the appearance of the GADRP was associated with clinical improvement.

"The current study indicates that customized networks can be characterized using functional imaging data acquired in randomized, controlled phase 2 clinical trials and, if validated, could be used as quantitative outcome measures in more definitive, later-stage clinical trials," the authors write.

The study was funded by Neurologix Inc., and two authors disclosed ties to Meira GTx.

Abstract/Full Text (subscription or payment may be required)

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