A Clinical Study of the Safety and Efficacy of Chemogenetics Therapy in the Treatment of Parkinson's Disease

Not Applicable

Not yet recruiting

• Conditions: Parkinson Disease (PD); Gene Therapy; Safety and Efficacy; Clozapine
• Interventions: Genetic: gene therapy; Drug: clozapine

• Registration Number: NCT07085195
• Lead Sponsor: Ruijin Hospital

Brief Summary

The investigators propose a gene therapy strategy using chemical genetic inhibition to intervene in the abnormal activity of the subthalamic nucleus in Parkinson's disease. The investigators design and construct a highly efficient therapeutic injection STP-001 (first drug), through the efficient adeno-associated virus capsid (AAV), neuronal promoter (hSyn), and chemical genetic effector element (hM4Di), and accurately inject the drug into the bilateral subthalamic nucleus, the core pathological nucleus of Parkinson's disease, through stereotactic technology. Combined with a very low dose of clozapine (the second drug), the abnormal activity of the subthalamic nucleus is precisely intervened to improve the core motor symptoms of Parkinson's disease.

Detailed Description

This is a single-arm and open-label study design for initial safety assessment. 6 cases of patients with iPD will be recruited from the neurology department of Ruijin Hospital, Affiliated Shanghai Jiao Tong University, School of Medicine. After the informed consent is signed, six participants will be divided into three dose groups in the dose escalation principle to receive the STP-001 injection. The virus dose escalation principle is as follows:

After the first sentinel subject receives 1×10¹² vg virus vectors, the research team will evaluate the safety, tolerability, and efficacy of the current drug dose after 4 weeks. If this sentinel does not experience dose-limiting toxicity, another sentinel subject will receive a 2×10¹² vg dose; if this sentinel develops dose-limiting toxicity (DLT), this dose will be defined as an intolerable dose, and the Data Review Committee will determine whether to select a lower dose for exploration or terminate dose escalation based on the existing data. If this sentinel subject doesn't experience dose-limiting toxicity, another subject will receive a 4×10¹² vg dose. If this sentinel subject doesn't experience DLT, all of the next three subjects will receive a 4×10¹² vg dose. 4 weeks After receiving the STP-001 injection, when the participants have recovered, clozapine ramp-up will be performed, and the participants will be treated orally with clozapine. Clozapine is 25 mg per tablet, and the oral dose is 1/32, 1/16, and 1/8 tablet twice a day, in the morning and at noon, respectively, with each dose repeated for 3 days for a total of 9 days. If no DLT develops during this time, the participants will continue to take 1/8 pill orally twice a day as a maintenance dose, and they will be monitored for 12 months.

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-15
• Study First Submitted QC: 2025-07-24
• Last Update Submitted: 2025-07-24
• Study First Posted: 2025-07-25
• Last Update Posted: 2025-07-25
• Study Start: 2025-08-01
• Primary Completion: 2025-12-30
• Study Completion: 2025-12-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
all of 6 patients plan to receive chemogenetic gene therapy	gene therapy	This is a single-arm and open-label study design for initial safety assessment. Six participants will be divided into three dose groups in the dose escalation principle. The dose escalation principle is as follows: After the first sentinel subject receives 1×10¹² vg virus vector, the research team will evaluate the safety, tolerability, and efficacy of the current drug dose after 4 weeks. If this sentinel does not experience dose-limiting toxicity, another sentinel subject will receive a 2×10¹² vg dose; if this sentinel develops dose-limiting toxicity (DLT), this dose will be defined as an intolerable dose, and the Data Review Committee will determine whether to select a lower dose for exploration or terminate dose escalation based on the existing data. If this sentinel subject doesn't experience dose-limiting toxicity, another subject will receive 4×10¹² vg dose. If this sentinel subject doesn't experience DLT, all of the next three subjects will receive 4×10¹² vg dose.
all of 6 patients plan to receive chemogenetic gene therapy	clozapine	This is a single-arm and open-label study design for initial safety assessment. Six participants will be divided into three dose groups in the dose escalation principle. The dose escalation principle is as follows: After the first sentinel subject receives 1×10¹² vg virus vector, the research team will evaluate the safety, tolerability, and efficacy of the current drug dose after 4 weeks. If this sentinel does not experience dose-limiting toxicity, another sentinel subject will receive a 2×10¹² vg dose; if this sentinel develops dose-limiting toxicity (DLT), this dose will be defined as an intolerable dose, and the Data Review Committee will determine whether to select a lower dose for exploration or terminate dose escalation based on the existing data. If this sentinel subject doesn't experience dose-limiting toxicity, another subject will receive 4×10¹² vg dose. If this sentinel subject doesn't experience DLT, all of the next three subjects will receive 4×10¹² vg dose.

Primary Outcome Measures

Name	Time	Method
1. The incidence of adverse events and serious adverse events within 12 months after bilateral subthalamic nucleus injection of STP-001, which is the adeno-associated virus vector carrying the target gene.	Electrocardiogram and laboratory tests will be conducted at baseline and then prior to, during, and after the neurosurgery operation and 4, 12, 24, 36, and 48 weeks after administration of the intervention.	Adverse events and serious adverse events will be assessed by electrocardiogram and laboratory tests for safety and tolerability assessment, including routine blood tests, routine urine tests, and blood biochemistry.
2. The changes in the titer levels of the binding and capsid-neutralizing antibodies against adeno-associated virus in serum within 12 months after bilateral subthalamic nucleus injection of STP-001.	The titer levels of binding and capsid-neutralizing antibodies will be conducted at baseline, at the time after the neurosurgery operation, and at 12, 24, 36, and 48 weeks after administration of the intervention.	The changes in the titer levels of the binding and capsid-neutralizing antibodies against adeno-associated virus in serum will be assessed for safety and tolerability assessment.

Secondary Outcome Measures

Name	Time	Method
The differences of the Non-Motor Symptoms Questionnaire before and after treatment	12, 24, 36, and 48 weeks	Compare the changes in the Non-Motor Symptoms Questionnaire from baseline to post-treatment in all of the 6 participants.
The differences of the Sniffin' Sticks 16-item Test and Pittsburgh Sleep Quality Index before and after treatment	12, 24, 36, and 48 weeks	Compare the changes in the Sniffin' Sticks 16-item Test and Pittsburgh Sleep Quality Index from baseline to post-treatment in all of the 6 participants.
The differences of the Mini-Mental State Examination before and after treatment	12, 24, 36, and 48 weeks	Compare the changes in the Mini-Mental State Examination from baseline to post-treatment in all of the 6 participants.
The differences of the Tinetti Performance Oriented Mobility Assessment before and after treatment	12, 24, 36, and 48 weeks	Compare the changes in the Tinetti Performance Oriented Mobility Assessment from baseline to post-treatment in all of the 6 participants.
The differences of the Berg balance scale before and after treatment	12, 24, 36, and 48 weeks	Compare the changes in the Berg balance scale from baseline to post-treatment in 6 participants.
The differences of the Webster Rating Scale before and after treatment	12, 24, 36, and 48 weeks	Compare the changes in the Webster Rating Scale from baseline to post-treatment in 6 participants.
The differences of anti-PD drug usage before and after treatment	The anti-PD drug usage will be conducted at baseline, at the time after the neurosurgery operation, and at 12, 24, 36, and 48 weeks.	Compare the changes in anti-PD drug use, including daily oral levodopa or a levodopa-equivalent dose, from baseline to post-treatment in 6 participants.
The differences of the Gait and Falls questionnaires before and after treatment	12, 24, 36, and 48 weeks	Compare the changes in the Gait and Falls questionnaires from baseline to post-treatment in all of the 6 participants.
The differences of the REM Sleep Behavior Disorder Screening Questionnaire before and after treatment	12, 24, 36, and 48 weeks	Compare the changes in the REM Sleep Behavior Disorder Screening Questionnaire from baseline to post-treatment in all of the 6 participants.
The differences of the Montreal Cognitive Assessment and Mini-Mental State Examination before and after treatment	12, 24, 36, and 48 weeks	Compare the changes in the Montreal Cognitive Assessment and Mini-Mental State Examination from baseline to post-treatment in all of the 6 participants.
The differences of the Hamilton Depression Scale before and after treatment	12, 24, 36, and 48 weeks	Compare the changes in the Hamilton Depression Scale from baseline to post-treatment in all of the 6 participants.
The differences of the Hamilton Anxiety Scale before and after treatment	12, 24, 36, and 48 weeks	Compare the changes in the Hamilton Anxiety Scale from baseline to post-treatment in all of the 6 participants.
The differences of the Parkinson's Disease Sleep Scale-2 before and after treatment	12, 24, 36, and 48 weeks	Compare the changes in the Parkinson's Disease Sleep Scale-2 from baseline to post-treatment in all of the 6 participants.
The differences of the Parkinson's Disease Questionnaire before and after treatment	12, 24, 36, and 48 weeks	Compare the changes in the Parkinson's Disease Questionnaire from baseline to post-treatment in all of the 6 participants.
The changes of the MRI before and after treatment	12, 24, 36, and 48 weeks	Compare the changes in the MRI examination, including BOLD-MRI, DTI, QSM, and NM-MRI, from baseline to post-treatment in 6 participants.
The differences of the MDS-Unified Parkinson's Disease Rating Scale before and after treatment	12, 24, 36, and 48 weeks	Compare the changes in the MDS-Unified Parkinson's Disease Rating Scale from baseline to post- treatment in all of the 6 participants.
The differences of the Patient Global Impression improvement scale before and after treatment	12, 24, 36, and 48 weeks	Compare the changes in the Patient Global Impression improvement scale from baseline to post-treatment in all of the 6 participants.
The differences of the Clinical Global Impression scale-improvement before and after treatment	12, 24, 36, and 48 weeks	Compare the changes in the Clinical Global Impression scale-improvement from baseline to post-treatment in all of the 6 participants
The differences of the Scales for Outcomes in Parkinson's Disease Autonomic before and after treatment	12, 24, 36, and 48 weeks	Compare the changes in the Scales for Outcomes in Parkinson's Disease Autonomic from baseline to post-treatment in all of the 6 participants.

Trial Locations

Locations (1)

Department of neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; 🇨🇳 Shanghai, China