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

NCT07533591 | Not Yet Recruiting Early Phase 1 DMC

• 1 other identifier: 2026-0355
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Parkinson's Disease (PD)

Keywords

Parkinson's Disease; Chemical Genetic Gene Therapy; subthalamic nucleus; clozapine

Outcome Measures

Primary Outcomes (1)

• The incidence rates of adverse events and serious adverse events within 3 months after injecting STP-001 into the bilateral subthalamic nuclei.

  Adverse events and serious adverse events will be evaluated through physical examinations, electrocardiogram tests and laboratory tests to assess their safety and tolerability, including routine blood tests, routine urine tests, imaging studies, etc. The main aspects include the occurrence of CRS and GvHD (≥ grade II), as well as injection-induced dyskinesia (GIDs), new-onset allogeneic tumors after injection, and death.

  3 months after injecting STP-001

Secondary Outcomes (9)

• The incidence rates of adverse events and serious adverse events within 12 months after STP-001 was injected into the bilateral subthalamic nuclei.

  12 months after STP-001

• The differences of the MDS-Unified Parkinson's Disease Rating Scale before and after treatment

  12 months after STP-001 injection

• The differences of the Clinical Global Impression scale-improvement before and after treatment

  12 months after STP-001 injection

• The differences of the Patient Global Impression improvement scale before and after treatment

  12 months after STP-001injection

• The differences of the Non-Motor Symptoms Questionnaire before and after treatment

  12 months after STP-001 injection

Study Arms (1)

STP-001 group

EXPERIMENTAL

This is a single-arm, open-label preliminary safety assessment study design. Six patients with iPD will be recruited from the Department of Neurology of the Second Affiliated Hospital of Zhejiang University School of Medicine. After signing the informed consent form, these 6 participants will be divided into 2 dose groups according to the dose escalation principle and receive the STP-001 injection solution. The virus dose escalation principle is as follows: After 3 sentinel subjects receive 1×10¹² volts of the virus vector, the research team will assess the safety, tolerance and efficacy of the current drug dosage 3 months later. If the test subjects do not show dose-limiting toxicity and have some efficacy, the sample size will be expanded to 6 at the original dosage. If the test subjects do not show dose-limiting toxicity but have no obvious efficacy, the titer will be increased to 3×10¹² volts and three more participants will be recruited for the trial. Four weeks after the inject

Genetic: gene therapy

Interventions

gene therapy GENETIC

Six participants are planned to be divided into two dose groups in the dose escalation principle. The dose escalation principle is as follows: After 3 sentinel subjects receive 1×10¹² volts of the virus vector, the research team will assess the safety, tolerance and efficacy of the current drug dosage 3 months later. If the test subjects do not show dose-limiting toxicity and have some efficacy, the sample size will be expanded to 6 at the original dosage. If the test subjects do not show dose-limiting toxicity but have no obvious efficacy, the titer will be increased to 3×10¹² volts and three more participants will be recruited for the trial. Four weeks after the injection of STP-001, when the participants recover, clozapine dose escalation treatment will be carried out.

STP-001 group

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 Parkinson's Disease Rating Scale (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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

Second Affiliated Hospital, School of Medicine,Zhejiang University

Zhejiang, Province, China

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Genetic Therapy

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Genetic Engineering; Genetic Techniques; Investigative Techniques

Study Officials

• Jiali Pu

  Second Affiliated Hospital, School of Medicine, Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiali Pu

CONTACT

+86-13989468062; Jialipu@zju.edu.cn

Yang Ruan

CONTACT

+86-18858736151; 11818236@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2026
• First Posted: April 16, 2026
• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2029
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)