Mild and moderate Alzheimers disease
Conditions
Interventions
Research group:CD73+NK cells(ZJ-S-0106)
Sponsors
Shenzhen Second People's Hospital
Eligibility
Sex/Gender
All
Age
50 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Age range: 50-80 years old (inclusive of 50 and 80). Gender is not restricted. 2. AD diagnostic indicators: Positive Abeta PET result, tau PET deposition (United States, NIA-AA 2024); 3. MRA of the brain vessels excluded the presence of hemangioma (except for those that have been treated); and there was no recurrence of cerebral infarction or cerebral hemorrhage within 3 months. 4. Cognitive function assessment indicates: The Minimum Mental State Examination (MMSE) score ranges from 10 to 26 points. Or the Montreal Cognitive Assessment (MoCA) score ranges from 19 to 25 points (applicable when the patient has mild cognitive impairment). 5. Expected survival time >= 6 months; 6. Patients voluntarily participate in systematic rehabilitation therapy; including, but not limited to, traditional occupational activity therapy, computer-assisted cognitive rehabilitation, virtual reality training, transcranial direct current stimulation, and transcranial magnetic stimulation. 7. Adequate organ and bone marrow function, defined as follows, was assessed during the screening period: (1) Blood count: Absolute Neutrophil Count (ANC) >=1.5 × 10^9/L, Platelet (PLT) >=90 × 10^9/L, Hemoglobin (HGB) >= 80 g/L (no blood transfusion or erythropoietin treatment within 14 days); (2) Liver function: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) levels = 60 mL/min (Cockcroft); (5) Cardiac function tests: Left ventricular Ejection Fraction (LVEF) >= 50%; Arrhythmia that does not require treatment, Fridericia's calibrated QT interval (QTcF) <= 470 ms [QTcF is calculated using the Fridericia formula, i.e., QTcF = QT / (RR^0.33), RR is the standardized heart rate value, RR = 60 / heart rate; if the first test is abnormal, repeat the test 2 times at an interval of at least 5 minutes, and then take the combined result/average to judge the eligibility]; (6) Fasting blood glucose and glycosylated hemoglobin levels are controlled at less than 120% of the upper limit of the normal level by drugs or non-drugs; blood lipids are controlled at less than 120% of the upper limit of the normal level by drugs or non-drugs; blood pressure is controlled at less than 120% of the upper limit of the normal level by drugs or non-drugs. 8. Patients with mild or moderate degrees of the disease, i.e., those with a total score of the Clinical Dementia Rating Scale (CDR) <= 2 points. 9. The Hachinski Ischemia Index Scale (HIS) score is <= 4 points. 10. The score of the Geriatric Depression Scale (GDS) ranges from 0 to 10 (including the boundary values). 11. Memory decline lasts for at least 12 months and shows a progressive worsening trend. 12. The subjects agreed to take effective contraceptive measures during the trial (the measures must be non-medical contraceptive methods). Women of childbearing age or patients with a post-menopausal period shorter than 24 weeks must undergo a pregnancy test during the screening period, and the result must be negative. 13. If the patient is currently receiving an AD treatment medication before the screening period, it is required that the dosage remains stable for at least 30 days prior to the screeni
Exclusion criteria
Exclusion criteria: 1. Dementia caused by other reasons: Frontotemporal dementia, Lewy body dementia, vascular dementia, dementia caused by Parkinson's disease, dementia caused by epilepsy, dementia caused by brain trauma, dementia related to central nervous system infections and immunity, etc. and there is active cerebral hemorrhage. 2. HIV-positive, HBsAg-positive with a positive HBV DNA copy number (>=1000 cps/mL by quantitative testing), HCV antibody-positive and HCV RNA-positive; 3. Those with mental or psychological illnesses who are unable to cooperate with treatment and efficacy assessment; 4. Subjects with severe autoimmune disease and long-term use of immunosuppressive agents; 5. Active or uncontrolled infection requiring systemic therapy within 14 days prior to enrollment; 6. Any unstable systemic disease (including, but not limited to): active infection (other than localized infection); unstable angina; symptomatic cerebrovascular ischemia or cerebrovascular accident (within 6 months prior to screening); myocardial infarction (within 6 months prior to screening); congestive heart failure (New York Heart Association [NYHA] classification >= Class III); severe arrhythmia requiring medication; uncontrolled hypertension (blood pressure > 160 mmHg/100 mmHg) with heart disease requiring treatment or after treatment; during the screening process, or previously had neurological disorders such as stroke, optic neuritis, epilepsy, etc. Glycated hemoglobin (HbA1c) >= 6.5%. 7. Combined dysfunction of vital organs such as lungs, brain, liver and kidney; 8. Subject has undergone major surgery or severe trauma within 4 weeks prior to receiving cell therapy, or is expected to undergo major surgery during the study period. 9. Subject is currently suffering from or has suffered from another malignancy that is incurable within 3 years, with the exception of cervical cancer in situ or basal cell carcinoma of the skin, and other malignancies with a disease-free survival of more than 5 years; 10. Received treatment with chimeric antigen receptor-modified T cells (including CAR-T, TCR-T) within six months; 11. Organ transplantation combined with graft-versus-host disease (GVHD); 12. Subjects who were receiving systemic steroid treatment before screening and for whom the investigator determined that long-term systemic steroid treatment was necessary during the study period (excluding inhalation or local use). And for the subjects who received systemic steroid treatment within 72 hours prior to cell infusion (excluding inhalation or local application); 13. History of severe allergies or sensitivities; 14. Subjects requiring anticoagulation therapy; 15. Women who are pregnant or breastfeeding, or who plan to become pregnant within six months (for both men and women); 16. There are contraindications for transcranial magnetic stimulation, magnetic resonance imaging or electroencephalogram (such as: pacemaker, cochlear implant, pulse generator, metal in the brain, scalp infection or trauma, etc.); 17. The researchers believe that there are other factors that prevent patients from being included in the treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| NCI CTCAE version 5.0; | — |
Secondary
| Measure | Time frame |
|---|---|
| ZJ-S-0106 Cell expansion and persistence in vivo;Imaging assessment;Score of the Neurological Rehabilitation Evaluation Scale; | — |
Countries
China
Contacts
Public ContactLiangXiao
Shenzhen Second People's Hospital
Outcome results
None listed