A Trial to Evaluate Safety and Efficacy of a Product Named VGN-R08b in Parkinson's Disease Patients With GBA1 Mutations

Exclusion Criteria

• •Subject has any of the following diseases or disease history
• •1. Patients with atypical or secondary parkinsonian syndromes, including but not limited to those caused by trauma, brain tumors, infections, cerebrovascular diseases, or other neurological disorders; or symptoms confirmed by the investigator to be induced by drugs, chemicals, or toxins; or those with other serious neurological conditions deemed by the investigator to significantly compromise the safety and efficacy evaluation of the investigational drug.
• •2. Patients with active infections (including viral infections such as HBV, HCV, or syphilis) or a history of severe infections within 12 weeks prior to screening (e.g., pneumonia, sepsis, or central nervous system infections such as meningitis or encephalitis).
• •3. Patients with severe liver disease, severe immunodeficiency, or autoimmune diseases within 6 months prior to screening, or those requiring long-term immunosuppressive therapy.
• •4. Patients with poorly controlled diabetes or hypertension, judged by the investigator as unsuitable for dosing or likely to substantially impact the efficacy and safety analysis of the investigational drug.
• •5. Patients with a history of stroke or transient ischemic attack (TIA), unstable angina, myocardial infarction, chronic heart failure (NYHA Class III or IV), or clinically significant conduction abnormalities (e.g., unstable atrial fibrillation) within 1 year prior to screening.
• •6. Patients with a history of epileptic seizures or unexplained coma, deemed unsuitable by the investigator for participation in the trial.
• •7. Patients with a history of severe allergic reactions, or hypersensitivity to any inactive ingredient of the investigational drug or to immunosuppressants required by the trial protocol.
• •8. Patients with contraindications to corticosteroids or sirolimus, including but not limited to osteoporosis with vertebral fractures within 1 year prior to screening, poorly controlled hyperlipidemia or hypercholesterolemia, renal insufficiency, or interstitial lung disease.
• •9. Patients with newly diagnosed or unstable psychiatric disorders within 1 year prior to screening that may interfere with trial procedures and evaluations, including confusion, severe depression (HAMD score \>35), or suicidal/self-harm tendencies.
• •10. Patients with a history of malignancy within 3 years prior to screening, except for completely resected non-melanoma skin cancer, non-metastatic prostate cancer, or fully cured carcinoma in situ that has remained stable for at least 6 months.
• •11. Patients with any other contraindications deemed by the investigator to potentially affect trial-related procedures, including lumbar puncture or intracerebral injection, such as spinal disorders, bleeding diathesis, clinically significant coagulation dysfunction, thrombocytopenia, or elevated intracranial pressure.