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

NCT07533591

Not Yet RecruitingEARLY_Phase 1

Sponsor: Second Affiliated Hospital, Zhejiang University, School of Medicine

Conditions: Parkinson's Disease (PD)

Interventions: gene therapy

Countries: China

The investigators propose a gene therapy strategy for Parkinson's disease - a chemogenetic inhibition technique to intervene in the abnormal activity of the subthalamic nucleus in Parkinson's patients. The investigators design and construct a therapeutic injection agent called STP-001, through an efficient adeno-associated virus capsid (AAV), a neuronal promoter (hSyn), and a chemogenetic effector element (hM4Di). Then, the drug was accurately injected into the bilateral subthalamic nuclei through stereotactic surgery. After the surgery, combined with clozapine, the abnormal activity of the subthalamic nucleus was precisely intervened to improve the core motor symptoms of Parkinson's disease.

Eligibility overview

Sex: ALL

Age: 40 Years to 70 Years

Healthy volunteers: No

Study type: INTERVENTIONAL

Eligibility criteria

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.

Locations (1)

Zhejiang, Province, China