Idiopathic Parkinson's Disease
Conditions
Interventions
Low dose group:GM101injection
High dose group:GM101injection
Sponsors
Xiangya Hospital,Central South Univerity
Eligibility
Sex/Gender
All
Age
40 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1.Clinically diagnosed patients with primary Parkinson's Disease [in accordance with the "Diagnostic Criteria for Parkinson's Disease in China" released in 2016]; 2.Participants must be able to comprehend (fully understand the details of the clinical trial and the potential risks and benefits of the study) and voluntarily sign the informed consent form. When participants are unable to read, the informed consent form and other written materials may be read by a legal representative or an impartial witness, who will also witness the consent process; 3.Age between 40 and 70 years old, inclusive, regardless of gender; 4.Body weight between 40 kg and 110 kg, and Body Mass Index (BMI) between 18 kg/m² and 34 kg/m²; 5.A history of Parkinson's Disease for >= 5 years; 6.Able to undergo surgical anesthesia, suitable for neurosurgical procedures under anesthesia, and capable of undergoing CT/MRI examinations; 7.Hoehn-Yahr stage (Appendix IV Hoehn-Yahr Staging) at screening in the "off" state is 3-4 (including borderline values); 8.MDS-Unified Parkinson's Disease Rating Scale Part III Motor Examination (MDS-UPDRS-III) score in the "off" state >= 30; and a positive levodopa challenge test (improvement in UPDRS-III score from "off" to "on" state >30%); 9.Patients whose PD symptoms cannot be effectively controlled or who experience intolerable adverse drug reactions despite treatment with medications recommended by the "Chinese Guidelines for the Treatment of Parkinson's Disease (4th Edition)-2020"; 10.Receiving a stable dose of anti-Parkinson's medication for at least 4 weeks prior to administration; 11.Acceptable laboratory values during the screening period and prior to administration (Day 0): a) Hemoglobin >= 100 g/L; b) Platelets >= 100×10^9/L; c) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <= 1.5 times the upper limit of normal; d) Total bilirubin <= 1.5 times the upper limit of normal; e) Serum creatinine (Cr) <= 1.5 times the upper limit of normal; 12.Participants agree not to receive any other therapeutic intervention studies during the main study phase; 13.Participants agree not to participate in any other clinical studies during the study period; 14.Participants agree not to receive any other vaccines within 30 days after administration; 15.Participants must have the ability to live independently or the ability to clearly delegate relevant caregivers, with good compliance, and be able to attend regular follow-ups. During follow-up, participants must accurately complete the PD patient diary, and family members, guardians, or caregivers may assist in filling out the patient diary; 16.Participants must have a pre-existing neutralizing AAV8 antibody titer <= 1:90 as determined by testing; 17.Based on the judgment of the Principal Investigator (PI), cancer-related screening will be conducted for patients who meet the inclusion criteria.
Exclusion criteria
Exclusion criteria: 1.Patients with atypical parkinsonian syndromes (Parkinson-plus syndromes, secondary Parkinson's syndrome, or hereditary Parkinson's syndrome). 2.Patients who have previously undergone pallidotomy, deep brain stimulation (DBS) surgery, striatal/extrapyramidal system surgery, stereotactic brain surgery, or other cerebral surgeries that might affect the observation of this trial's outcomes; or those who have undergone other surgeries deemed by investigators to interfere with study participation. 3.Patients with intracranial lesions revealed by previous CT/MRI scans, such as cerebral trauma, cerebrovascular malformations, hydrocephalus, brain tumors, or striatal/other brain region abnormalities that significantly increase surgical risks. 4.Patients with history of the following cardiovascular/cerebrovascular diseases: 1)Severe heart failure, unstable angina, or myocardial infarction; 2)Severe arrhythmias including but not limited to II/III-degree atrioventricular block or prolonged QT interval; 3)Long QT syndrome; 4)Cardiovascular surgery history; 5)History of stroke or transient ischemic attack (TIA) within 3 months, deemed ineligible by investigators; 6)Subarachnoid hemorrhage history; 7)Major vascular diseases considered ineligible by investigators. 5.Patients with history of malignant tumors. 6.Patients who have received cell therapy. 7.Patients who have received gene therapy. 8.Patients with active disseminated intravascular coagulation or significant bleeding tendency within 3 months prior to consent, or those unable to discontinue antiplatelet/anticoagulant medications >= 7 days pre-operation, or whose coagulation function hasn't normalized >= 10 days after stopping antiplatelet medications. 9.Patients who received prolonged >= 14 days) high-dose systemic corticosteroids (prednisone >= 20 mg/day or equivalent) or immunosuppressants within 3 months prior to consent (topical use excluded). 10,Patients with psychiatric disorders deemed ineligible by investigators; or those with suicidal ideation/attempts (including actual attempts, interrupted attempts, or aborted attempts) within the past year or currently. 11.Patients who received botulinum toxin treatment within 6 months prior to consent. 12.Patients with active epilepsy or currently using antiepileptic drugs. 13.Patients with dementia or severe cognitive impairment history; or those showing significant dementia/cognitive dysfunction during screening; MDS-UPDRS Part 1.1 cognitive impairment score >3; dementia affecting compliance, diary accuracy, and/or informed consent capability. 14. Individuals with severe depression (Hamilton Depression Rating Scale [HAM-D17] score >= 24) or severe anxiety (Hamilton Anxiety Rating Scale [HAMA] score >= 29) during screening. 15. Individuals with the following clinically significant abnormalities during screening: 1) Abnormal coagulation function (prothrombin time >= 1.5 times the upper limit of normal, activated partial thromboplastin time >= 1.5 times the upper limit of normal); 2) Clinically significant immunological abnormalities, deemed unsuitable for participation by the investigator; 3) Poorly controlled hypertension (defined as blood pressure remaining above 160/100 mm Hg despite antihypertensive treatment) and severe orthostatic hypotension; 4) Poorly controlled diabetes (glycated hemoglobin > 9.0%, or fasting plasma glucose [FPG] >= 11.1 mmol/L). 16. Individuals with surgical contraindications (e.g., prior cochlear implant, pacemaker, de
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The incidence and severity of adverse events (AEs) related to surgery and/or investigational product;The incidence and severity of AEs/serious adverse events (SAEs); | — |
Secondary
| Measure | Time frame |
|---|---|
| Changes in the MDS-UPDRS-III scores of subjects during the "off" and "on" medication periods compared to baseline;Changes in the oral levodopa equivalent dose of subjects compared to baseline;Changes in motor fluctuations of subjects, such as the duration of "on" and "off" periods without dyskinesia, or with or without troublesome dyskinesia;Changes in the MDS-UPDRS-I, MDS-UPDRS-II, and MDS-UPDRS-IV scores of subjects compared to baseline;Changes in the PGI-I and CGI-I scores of subjects compared to baseline;Changes in the MMSE scores of subjects compared to baseline;Changes in the GDS scores of subjects compared to baseline;Changes in the PDSS-2 scores (assessing sleep quality) of subjects compared to baseline;Changes in the PDQ-39 scores (assessing quality of life) of subjects compared to the preoperative baseline;Changes in the signal intensity of C-CFT-PET (DAT imaging) in the putamen region of the brain (non-FDG) using PET/CT local tomography imaging; | — |
Countries
China
Contacts
Public ContactZhiquan Yang
Xiangya Hospital,Central South Univerity
Outcome results
None listed