Gene Therapy for Parkinson Disease: Where Do We Stand?

Insertion of the glutamic acid decarboxylase gene into the subthalamic nuclei resulted in significant motor improvement compared with sham surgery.

The standard of care for surgically treating patients with Parkinson disease (PD) is deep brain stimulation (DBS), wherein electrical stimulation of the subthalamic nucleus (STN) diminishes its output, thus freeing the ventrolateral thalamus and associated thalamocortical motor circuitry from the STN's indirect modulatory influence. However, DBS does not improve all PD symptoms. In an industry-supported, double-blind, randomized trial of gene therapy for PD, researchers used a viral vector to insert the gene for glutamic acid decarboxylase (GAD) into the STN. GAD is the rate-limiting enzyme in the synthesis of γ-aminobutyric acid (GABA), the neurotransmitter in afferent STN terminals. Augmenting GABAergic transmission attenuates the output …

Reviewing Author

Michael Hutchinson, MD