ZR001 Chemogenetics Gene Therapy Study in Patients With Parkinson's Disease

Laborértékek

• 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.

• 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.