Tests gene therapy ZR001 for Parkinson's disease by brain injection

Trial details

Who runs it

Qianfoshan Hospital

Trial code

NCT07718659

Record updated

22 July 2026

Original description

This study aims to evaluate the safety, tolerability, and preliminary efficacy of ZR001, a novel chemogenetic gene therapy product, in patients with moderately advanced Parkinson's disease (PD). ZR001 is administered via stereotactic injection into the bilateral substantia nigra, followed by postoperative ultra-low-dose clozapine to activate the transduced direct pathway, with the goal of improving motor symptoms of Parkinson's disease.Read full original descriptionShow less

An Open-label, Single Arm, Dose-Escalation Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of ZR001, a Gene Therapy Based on Chemogenetics, for the Treatment of Parkinson's Disease

This study aims to evaluate the safety, tolerability, and preliminary efficacy of ZR001, a novel chemogenetic gene therapy product, in patients with moderately advanced Parkinson's disease (PD). ZR001 is administered via stereotactic injection into the bilateral substantia nigra, followed by postoperative ultra-low-dose clozapine to activate the transduced direct pathway, with the goal of improving motor symptoms of Parkinson's disease.

Inclusion: Participants who meet all of the following criteria are eligible for enrollment:; Age ≥40 and ≤70 years (at the time of signing the informed consent), any gender; Diagnosed with Parkinson's disease according to the Diagnostic Criteria for Parkinson's Disease in China (2016 edition); Modified Hoehn \& Yahr stage between 2.5 and 4; History of Parkinson's disease for at least 5 years but less than 15 years; Moderate to severe MDS-UPDRS Part III score in the off period, and improvement rate ≥30% after acute levodopa stress test; Clinically stable symptoms and stable types and doses of anti-Parkinsonian medications within 3 months prior to enrollment; Agree to provide biological samples required for the study (e.g., blood, urine); Consent to hospitalization for intraparenchymal drug injection surgery; Male or female participants of childbearing potential agree to use effective contraceptive methods (oral contraceptives are prohibited) from the time of signing the informed consent until at least 6 months after discontinuing clozapine; Participants or their stable caregivers are able to understand and willing to comply with the study requirements and procedures, voluntarily participate, and sign the informed consent. If a caregiver is present, they must accompany the participant to study visits and assist the investigator in completing relevant scale assessments.

Exclusion: Participants who meet any of the following criteria will be excluded from this study:; Have participated in or are currently participating in other clinical studies of PD drugs or other AAV gene therapy or cell therapy; Presence of other severe psychiatric disorders (e.g., severe depression, schizophrenia, etc.); Previous adverse reactions to clozapine, such as agranulocytosis or severe neutropenia; Participants with known allergic constitution, including allergy or hypersensitivity to clozapine, prednisone acetate, other glucocorticoids, their excipients, or local anesthetics; History of alcohol or drug abuse within the past 2 years; Participants requiring invasive or non-invasive ventilatory support; Serum AAV binding antibody titer >1:2000; Presence of clinically significant laboratory abnormalities as assessed by the investigator: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin; creatinine, hemoglobin (Hb), prothrombin time (PT), activated partial thromboplastin time (APTT), fasting blood glucose, platelets (PLT); Presence of liver disease, heart disease, kidney disease or history thereof, which, in the investigator's assessment, may pose surgical or drug-related risks to the participant; Suffering from autoimmune diseases or immunocompromised status requiring hormone or immunosuppressive therapy, which, in the investigator's assessment, may pose surgical or drug-related risks; Suffering from other severe systemic diseases (e.g., cor pulmonale, moderate-to-severe asthma, etc.) that, in the investigator's assessment, may pose surgical or drug-related risks; In the investigator's assessment, the participant has contraindications to anesthesia or surgery and is unsuitable for intraparenchymal administration, or other special circumstances; Positive for human immunodeficiency virus antibody, hepatitis B surface antigen, hepatitis C antibody, syphilis antibody, active TORCH virus infection, or active Epstein-Barr virus infection; Concomitant use of any of the following medications within 90 days prior to administration, or planned immunosuppressive therapy (cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab) within 6 months after start of the trial, except for prophylactic medications specified in the protocol; Pregnant or breastfeeding women, or those planning to become pregnant; Other conditions that, in the investigator's opinion, make the participant unsuitable for participation in this study.

ClinicalTrials.gov NCT07718659