Glutamic acid decarboxylase (GAD) gene delivered to the subthalamic

Class

AAV gene therapy encoding the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD), bilateral stereotactic infusion into the subthalamic nucleus (STN)

Pathway

Restores local GABA production in the STN, normalizing GABAergic inhibitory input and reducing pathological overactivity of the STN that drives motor symptoms in Parkinson's disease

Notes

original target text: Glutamic acid decarboxylase (GAD) gene delivered to the subthalamic nucleus

Glutamic acid decarboxylase (GAD) is the enzyme that converts the excitatory neurotransmitter glutamate into gamma-aminobutyric acid (GABA), the principal inhibitory signaling molecule in the brain. In Parkinson's disease, loss of dopamine-producing neurons disrupts the basal ganglia circuitry that governs movement, leading to abnormal overactivity of the subthalamic nucleus (STN), a small structure that normally provides balanced excitatory drive within this circuit. This overactivity contributes to the tremor, rigidity, and slowed movement characteristic of the disease. The gene therapy approach uses an adeno-associated virus (AAV), a non-replicating viral vector commonly used to deliver genetic material into cells, to introduce the GAD gene directly into STN neurons via stereotactic surgical infusion (precise, image-guided injection into a specific brain target). Once expressed, GAD enables these neurons to produce GABA locally, shifting the STN's output from excitatory to inhibitory and thereby dampening its pathological hyperactivity. This strategy is relevant broadly to neurodegenerative and circuit-based movement disorders where restoring inhibitory balance within specific brain nuclei may improve motor control, offering a potentially durable, localized alternative to systemic pharmacological or electrical neuromodulation approaches.