A Clinical Study of the Safety and Efficacy of Chemogenetics Therapy in the Treatment of Parkinson's Disease

Korábbi kezelés

• Contraindications to surgery or previous deep brain stimulation surgery, pallidotomy, extrapyramidal surgery, other brain surgeries, or other neurosurgery that the researcher determines will affect their participation in this trial;
• Previous cranial imaging suggests abnormal brain structure, cerebrovascular malformations, intracranial tumors, intracranial hemorrhage risk, brain trauma, and other abnormalities;
• Participating in other clinical trials or having participated in other clinical trials within 3 months before the screening period;
• Having received gene therapy before being enrolled into this trial;
• Having received stem cell therapy within 6 months before the screening period;
• Having used other investigational drugs within 4 weeks before screening or within 5 half-lives of the investigational drug (whichever is longer), or drugs that the investigator determines affect this trial;
• Having received live vaccines within 2 months before the screening period or having a history of vaccination within 30 days before the screening period;
• Severe motor complications after anti-PD drug treatment and no suitable alternative treatment options;

Más betegség

• Atypical or secondary Parkinson's syndrome (such as Parkinson's plus syndrome, hereditary Parkinson's syndrome, drug-induced Parkinson's syndrome);
• Undergoing antiviral treatment for hepatitis B and hepatitis C;
• Suffering from malignant tumors or having a history of malignant tumors;
• Having had severe allergic reactions, allergic to contrast agents, or being unable to accept surgical anesthesia;
• Have a history of alcohol dependence or drug addiction and cannot stop drinking as advised by the doctor during the trial;

Laborértékek

• Abnormal liver and kidney function: Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 1.5 times the upper limit of normal value, serum creatinine (Cr) >1.5 times the upper limit of normal value;
• Infectious disease screening: Hepatitis B surface antigen (HBsAg) or hepatitis B virus DNA (HBV-DNA) positive, hepatitis C virus RNA (HCV-RNA) positive, human immunodeficiency virus (HIV) positive, or syphilis serum positive;
• Suffering from unstable or severe other systemic diseases: including active tuberculosis, cardiovascular system, respiratory system, Diseases of the digestive system, urinary system, mental and nervous system (such as epilepsy), blood system, immune system, etc., or abnormal laboratory test values, the investigator determines that the patient is not suitable for participating in this trial;

Egyéb

• If any of the following criteria are met, the patient shall be excluded from this study:
• Mini-Mental State Examination (MMSE) score <24 points;
• Montreal Cognitive Assessment (MoCA) score <26 points;
• Mini-Mental State Questionnaire (PHQ-9) ≥16;
• Abnormal coagulation function or using anticoagulants;
• Female subjects who are pregnant or breastfeeding;
• Subjects who are assessed by the researchers as unsuitable for inclusion.

• Participants who meet all the following criteria can be included in this clinical study:
• Clinically diagnosed with idiopathic Parkinson's Disease [in accordance with the Diagnostic Criteria for Parkinson's Disease in China published in 2016, or in accordance with the Diagnostic Criteria for Primary PD of the International Parkinson's and Movement Disorders Society (MDS) in 2015];
• Subjects aged 40-65 years old (including the boundary value), regardless of gender;
• Medical history of disease ≥5 years;
• Hoehn-Yahr staging scale for "off" period is 2.5-4;
• Regular use of dopaminergic drugs before the screening period, including taking levodopa for at least 4 weeks;
• MDS-UPDRS III score >35 in the "off" period, and the improvement rate of acute levodopa stress test ≥30%;
• AAV neutralizing antibody titer ≤1:2000;
• The subject agrees to postpone other neurosurgery during the main study phase (including deep brain stimulation, except for sudden life-threatening conditions requiring neurosurgery during the trial);
• No acute adverse reactions to the scheduled therapeutic dose of clozapine (1-month observation period);
• The subject agrees not to participate in other therapeutic intervention studies during the trial;
• The subject agrees not to be vaccinated during the study phase;
• Use reliable contraceptive methods from the screening period to at least 8 weeks after drug infusion;
• The subject has good compliance and can follow up regularly. During the follow-up period, the PD patient diary can be accurately completed. Family members, guardians, or caregivers can help the subject fill in the patient diary;
• The subject fully understands the nature, purpose, methods, and possible adverse reactions of this clinical trial, voluntarily participates as a subject, and signs the informed consent form; if the subject is unable to read, the legal agent or impartial witness can read the informed consent form and other written materials and witness the informed consent.