The Safety and Tolerability of XS411CN Injection in Treatment of Primary Parkinson's Disease

Inclusion criteria

• Male or female, aged between 50 and 75 years old;
• Diagnosed as 'clinically established PD' consistent with MDS clinical Diagnostic Criteria for Parkinson's disease,
• A minimum of 5 years since diagnosis;
• Hoehn- Yahr score during the off-time is 3 to 4;
• The subjects with an average of at least 2.5 hours of "off time" per day;
• Stable anti-PD therapy for at least 1 month before screening;
• Anti-PD treatment was once effective, but the efficacy has declined significantly or drug-induced motor complications have occurred, affecting the quality of life;
• Positive levodopa challenge test (MDS-UPDRS-III score improvement from off- state to on- state \> 30%);
• At least three months before the first administration, the subject should have completed all vaccinations as recommended by local authorities;
• The results of complete blood count meet the following conditions: ANC ≥ 2.0×109 /L, WBC ≥ 4.0×109 /L, PLT≥ 100×109 /L, HGB ≥ 10g/dL
• The patient or his/her legal guardian agree to accept the study and signed the informed consent form in writing.

Exclusion criteria

• Parkinsonian syndrome or secondary Parkinson's disease (Atypical Parkinson's syndrome (Parkinson's plus syndrome, secondary Parkinson's syndrome, hereditary degenerative Parkinson's syndrome);
• Patients are in advanced stages of Parkinson's disease and are experiencing severe, disabling peak-dose dyskinesia or biphasic dyskinesia and/or unpredictable or widely fluctuating symptoms;
• Severe cognitive impairment (MMSE\<24, poor compliance due to dementia, inability to accurately record diaries, and/or inability to sign informed consent;
• Those with a history of severe mental illness, or those with severe suicidal tendencies as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS), or those with suicidal ideation in the past 12 months, or those who have attempted suicide in the past 5 years;
• Patients with severe brain atrophy, space-occupying lesions, hydrocephalus, cerebral vascular malformations as indicated by head CT/MRI, and those with structural abnormalities that may affect transplantation or increase surgical risks as determined by the investigators;
• Currently with active internal bleeding; or arterial puncture at a site that is difficult to stop bleeding within 1 week before screening; or gastrointestinal or urinary bleeding within 3 weeks before screening;
• History of striatal or extrapyramidal surgery, including but not limited to deep brain stimulation (DBS) surgery and globus pallidus lesion;
• Coagulation abnormalities;
• Abnormal liver and kidney function laboratory tests during the screening period;
• The patient is currently receiving or has previously received the following treatments:
• Use of benzodiazepines at a dose level equal to or higher than the recommended dose in Package Insert for more than 4 weeks cumulatively since one month before enrollment, immunosuppressants (except for the immunosuppressants to be used in this study), or antipsychotics within 3 months before treatment;
• Use of botulinum toxin, phenol, subarachnoid baclofen injection, or interventional treatment for dystonia or spasticity within 6 months before treatment;
• Have a history of epilepsy or use anti-epileptic drugs for prevention;
• Received cell therapy within 3 months before screening;
• Contraindications to general anesthesia or stereotactic surgery (such as sleep apnea, chronic obstructive pulmonary disease, etc.), MRI or PET examinations;
• Those with the following abnormalities in the past or detected (if any of the following is met, they will be excluded):
• Evidence of congestive heart failure or history of end-stage cardiovascular disease;
• Severe arrhythmias and poorly controlled arrhythmias;
• Clinically significant electrocardiogram abnormalities during the screening or baseline period;
• History of unstable angina or acute myocardial infarction within the past 3 months;
• Diabetic patients with poor glycemic control;
• Hypertensive patients with poorly controlled blood pressure;
• Patients with active infection during the screening period (except mild local skin infection) that need antibiotic, antifungal, or antiviral treatment but infection is still not under control;
• The presence of severe lung diseases during the screening period;
• Patients with uncontrolled autoimmune diseases;
• During the screening period, patients have severe arthritis, limp, severe sequelae of stroke, severe osteoporosis, or history of severe trauma within 1 month, etc., which the investigators assess may affect the evaluations;
• Any history of malignancy, excluding cured basal cell carcinoma and/or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or ductal carcinoma of the breast;
• Serious infectious diseases;
• Pregnant or lactating women, women who plan to become pregnant during the study and within 6 months after the end of the study, or women who are unwilling to use effective contraceptive measures;
• Patients who have participated in other clinical studies of drugs or medical devices within 3 months before treatment;
• Have a long history of alcoholism or drug abuse;
• Patients with a history of severe allergies or allergies to investigational drugs and immunosuppressants;
• Any other conditions that the investigator considers unsuitable for participation in the study.
• Severe depression
• Hallucinations, and hallucinations still exist after optimizing Parkinson's medications
• Patients have undergone MRI-guided focused ultrasound thalamotomy
• Used immunosuppressants within 3 months, except for the immunosuppressants to be used in this study