One-Time brain injection targets genetic form of Parkinson's

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Aged 30 to 70 years inclusive; both males and females are eligible. 2. The participant fully understands the purpose, nature, procedures of the study and potential adverse events, voluntarily agrees to take part in the study and signs the informed consent form (ICF). 3. Participants with clinically diagnosed idiopathic Parkinson's disease (PD) meeting the 2015 Movement Disorder Society (MDS) diagnostic criteria for idiopathic PD. 4. Participants carrying at least one pathogenic GBA1 variant. 5. Duration of PD disease ≥ 3 years. 6. Off-state Hoehn-Yahr stage ranges from 2.5 to 4. 7. Neutralizing antibody titer against AAV ≤ 1:200. 8. The off-state MDS-UPDRS Part III (see Appendix 6 for MDS-UPDRS Part III motor examination) score is greater than 25, with either a ≥30% improvement rate on the acute levodopa challenge test, or an average daily off time of ≥2.5 hours over 3 consecutive days. 9. Investigators determined that patients must receive a stable dose of dopaminergic medications, including levodopa, for a minimum of 4 weeks prior to surgery. 10. Acceptable laboratory test values shall be obtained during the screening period and prior to administration (Day -3)：a).Hemoglobin ≥ 100 g/L; b).Platelets ≥ 100 × 10⁹/L; c). Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) ≤ 2 × upper limit of normal (ULN); d).Total bilirubin ≤ 2 × upper limit of normal (ULN); e).Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min. 11. Demonstrates good treatment adherence and ability to attend scheduled follow-up visits; the participant shall be capable of accurately completing the Parkinson's disease (PD) diary during follow-up, or the participant's family member, legal guardian or caregiver may assist with diary completion. 12. The participant agrees to postpone any other planned elective neurosurgical procedures (excluding emergent life-threatening neurosurgical operations occurring during the study), including Deep Brain Stimulation (DBS), until completion of the 52-week follow-up period, unless DBS treatment is recommended by a specialist in the participant's best interest. 13. The participant agrees not to participate in any other therapeutic intervention studies during the study period and shall not take any other medications that may interfere with treatment other than those specified in the protocol. 14. The participant agrees to refrain from receiving any vaccinations within 30 days after surgery. 15. The participant must be willing to refrain from donating blood, organs, tissues or cells at any time following treatment administration. 16. Female participants of childbearing potential (WOCBP) must have a negative pregnancy test. 17. The participant and their partner have no plans to conceive from screening through 6 months after study completion, and will voluntarily use effective contraceptive measures (such as abstinence, condoms, etc.); the participant has no intention to donate sperm or ova. Exclusion Criteria: 1. Atypical or secondary parkinsonism (including Parkinson-plus syndromes, hereditary parkinsonism, drug-induced parkinsonism, etc.). 2. Patients with clinically confirmed LRRK2 mutation. 3. Previous history of pallidotomy, Deep Brain Stimulation (DBS) surgery, striatal surgery, extrapyramidal surgery, stereotactic brain surgery or other brain surgeries; or any other surgical history judged by the investigators to interfere with the subject's participation in this study. 4. Participants with previous head Computed Tomography (CT) / Magnetic Resonance Imaging (MRI) showing neurological diseases such as brain trauma, vascular malformations, hydrocephalus, brain tumors; subjects with hyperintense white matter signals on MRI indicating risk of intracranial hemorrhage; subjects with cerebrovascular lesions or microbleeds on SWI (Susceptibility-Weighted Imaging); subjects with vulnerable plaques or intraplaque hemorrhage of craniocervical arteries on HR-MRI (High-Resolution Magnetic Resonance Imaging); or subjects with imaging abnormalities in the striatum or other brain regions that substantially increase surgical risks. 5. The participant has a Mini-Mental State Examination (MMSE) score of less than 20. 6. A Patient Health Questionnaire (PHQ) score of ≥16 indicates severe depression. 7. Any severe psychiatric illnesses including epilepsy, severe anxiety, schizophrenia that are deemed unsuitable for participation in this study by the investigators, excluding mild hallucinations and similar symptoms induced by anti-Parkinsonian medications. 8. Patients taking anticoagulants or antiplatelet drugs whose coagulation function has not returned to normal 10 days after drug discontinuation. 9. Patients who have previously received gene therapy or cell therapy. 10. Use of systemic glucocorticoids or immunosuppressive drugs within 12 weeks prior to administration, except for prophylactic immunosuppressive agents required by the protocol (excluding prophylactic immunosuppressive therapy specified in the protocol). 11. Participants with unstable cardiovascular and cerebrovascular diseases, defined as clinical cardiovascular and cerebrovascular events occurring within 3 months prior to screening (e.g., unstable angina, myocardial infarction, stroke, etc.); uncontrolled diabetes mellitus with glycated hemoglobin \>8.0%; or other unstable acute or chronic diseases including infectious diseases, severe uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg), or severe orthostatic hypotension (a drop in systolic blood pressure ≥20 mmHg or diastolic blood pressure ≥10 mmHg within 3 minutes after the participant changes from supine/squatting position to standing position). 12. Positive Hepatitis B surface antigen (HBsAg) or Hepatitis B Virus Deoxyribonucleic Acid (HBV-DNA); positive Hepatitis C Virus antibody (HCV-Ab) or Hepatitis C Virus Ribonucleic Acid (HCV-RNA).For participants with a prior history of hepatitis B or hepatitis C, two samples collected at an interval of at least 3 months must test negative for all above indicators to be considered negative. Participants with spontaneously cleared or antivirally treated cleared hepatitis B or C are eligible for this study.Participants with positive Human Immunodeficiency Virus (HIV) test or positive syphilis serology. 13. Participants with surgical contraindications, those who have received other surgical procedures deemed to interfere with this study by the investigators within six months, or those with other contraindications to neurosurgery. 14. Participants with an average weekly alcohol intake exceeding 21 units for males or 14 units for females within 30 days prior to screening; 1 alcohol unit equals one 5 oz (150 mL) glass of red wine, 12 oz (360 mL) beer, or 1.5 oz (45 mL) distilled spirits; or participants with a history of drug dependence. 15. Participants with contrast medium allergy who cannot undergo MRI, or those unable to tolerate surgical anesthesia. 16. Participants with hypersensitivity to LY-N001 Injection. 17. History of cancer within 5 years prior to screening, excluding completely resected non-melanoma skin cancer, non-metastatic prostate cancer, fully cured carcinoma in situ, and papillary thyroid carcinoma cured after radical surgical resection. 18. Pregnant women, women planning pregnancy, or breastfeeding women. 19. Participants who are currently enrolled in another clinical trial, or those who participated in another clinical trial and received investigational products within one month. 20. Participants who are deemed ineligible for enrollment upon investigator's assessment.