Clinical Study of Chemogenetic Gene Therapy With AAV for Parkinson's Disease Using Stereotactic Surgery in the Subthalamic Nucleus

Inclusion Criteria: * Age range: 40 - 70 years (inclusive), gender not restricted; * Diagnosed with primary Parkinson's disease, with H\&Y grade ranging from 4 to 5; * Disease duration of at least 5 years; * Response to levodopa treatment lasting for at least 12 months; * Score of the third part of the MDS-UPDRS Part III ≥ 35; * Improvement rate of the Madopar challenge test ≥ 30%; * Stable clinical symptoms and drug treatment for at least 4 weeks before screening; * Capable of understanding and voluntarily signing the informed consent form; * Participants agree to postpone any neurological surgery, including deep brain stimulation, until the completion of 12-month follow-up; * The efficacy of dopamine drugs has significantly decreased, or there are obvious motor complications, or severe drug side effects; * There are no acute adverse reactions to the prescribed olanzapine dose; * Good compliance and willing to complete all the follow-up as stipulated in this protocol. Exclusion Criteria: * Has a past history of brain surgery for Parkinson's disease, such as deep brain stimulation, or other abnormal brain imaging findings; * Hamilton Depression Scale score ≥ 20; * Hamilton Anxiety Scale score ≥ 14 * Has a history of brain injury or central nervous system infection; * MoCA cognitive impairment score \< 26 points, and MMSE dementia rating scale cognitive impairment score ≤ 20 points; * Focal neurological deficits; * Evidence of major medical or mental illness, such as dementia, psychosis, history of drug abuse or severe depression; * Atypical Parkinson's disease or secondary Parkinson's disease caused by factors such as trauma, brain tumor, infection, cerebrovascular disease, other neurological diseases or drugs, chemicals or toxins; * Received other gene or cell therapy drugs; * Has a history of malignant tumors, but not including treated carcinoma in situ, or medical conditions that are poorly controlled and may increase the risk of surgery; * Has a history of stroke, or obvious cardiovascular diseases, diabetes; * Clinically obvious or laboratory-detected infections; * Chronic immunosuppressive therapy, including chronic steroids, immunotherapy, cytotoxic therapy and chemotherapy; * Coagulation disorders or inability to temporarily stop any anticoagulant or antiplatelet treatment before surgery; * Severe liver disease (AST/ALT ≥ 2.5 times the upper limit of normal (ULN)); * Any factor that may prevent the subject from following the study protocol, including medical or social factors, including geographical inconvenience; * Any other situation that the investigator deems unsuitable for participation in this study.