hUC-MSC-sEV-001 Nasal Drops for Neurodegenerative Diseases

General Criteria:

Inclusion Criteria:

1. Age 18-80 years (inclusive), any gender.

2. Subjects or their legal guardians voluntarily sign a written informed consent formand are able to comply with the study requirements for dosing and follow-up.

Exclusion Criteria:

1. Subjects who have received allogeneic mesenchymal progenitor cell therapy or itsderived small extracellular vesicles.

2. Subjects with abnormal nasal anatomy, nasal damage, severe rhinitis, or other nasalconditions that may affect the administration of the investigational product.

3. Subjects requiring nasogastric tube insertion.

4. Suffering from other uncontrolled diseases that may interfere with the studyresults, including but not limited to severe local infection, systemic infection, orimmunodeficiency.

5. Combined with malignant tumors, hematological malignancies, or other serioussystemic diseases.

6. Clinically significant history of allergic reactions, especially drug allergicreactions.

7. Severe renal insufficiency: creatinine clearance (CrCl) < 30 mL/min (calculated byCockcroft-Gault formula), or other known severe renal diseases.

8. Peripheral blood hemoglobin (HGB) < 100 g/L, absolute neutrophil count (NEUT) < 1.5 × 10⁹/L, platelet count (PLT) < 100 × 10⁹/L, white blood cell count (WBC) < 4.0 × 10⁹/L or ≥ 12 × 10⁹/L, serum albumin < 30 g/L; alanine aminotransferase (ALT) andaspartate aminotransferase (AST) ≥ 3 × upper limit of normal (ULN).

9. HBsAg positive, or HBcAb positive with HBV DNA positive, hepatitis C virus (HCV)antibody positive, peripheral blood HCV RNA positive, HIV antibody positive; CMV DNApositive, syphilis serology positive.

10. Contraindications to MRI examination (e.g., metal implants) or inability to tolerateMRI (e.g., claustrophobia).

11. Women of childbearing potential not intending to use effective contraception duringthe trial or within 90 days after the last dose and with a positive pregnancy testrecord; pregnant or lactating women; men who are sexually active during the trial orwithin 90 days after the last dose and not intending to use effective contraception;or men planning to donate sperm during the trial or within 90 days after the lastdose.

12. Vaccination within 1 month prior to the first dose or planned during the period fromenrollment until the end of follow-up.

13. Participation in other clinical drug studies within the past 30 days.

14. Any condition that, in the investigator's judgment, may compromise the subject'sability to understand and/or comply with the study procedures and/or follow-up.

Alzheimer's Disease (AD) Specific Criteria:

Inclusion Criteria:

1. Probable AD as defined by the 2011 National Institute on Aging-Alzheimer'sAssociation (NIA-AA) criteria.

2. Clinical Dementia Rating (CDR) score ≤ 1.0.

3. Subjects have an identified, reliable caregiver.

4. Stable treatment regimen for at least 1 month prior to dosing.

Exclusion Criteria:

1. Major history of significant brain injury with persistent neurological impairment (with or without) or known structural brain abnormalities.

2. Cognitive impairment due to other causes: central nervous system infection,Creutzfeldt-Jakob disease, traumatic dementia, other physical/chemical factors (e.g., drug intoxication, alcoholism, carbon monoxide poisoning), major systemicillnesses (e.g., hepatic encephalopathy, pulmonary encephalopathy), intracranialspace-occupying lesions (e.g., subdural hematoma, brain tumor), endocrine disorders (e.g., thyroid disease, parathyroid disease), vitamin B12 or folate deficiency, orany other known causes.

Parkinson's Disease (PD) Specific Criteria:

Inclusion Criteria:

1. Diagnosis of PD according to the 2015 Movement Disorder Society (MDS) clinicaldiagnostic criteria for PD.

2. Hoehn and Yahr stage ≤ 3.

3. Stable treatment regimen for at least 1 month prior to dosing.

Exclusion Criteria:

1. Parkinsonism other than PD, including but not limited to progressive supranuclearpalsy (PSP), multiple system atrophy (MSA), vascular parkinsonism, drug-inducedparkinsonism, essential tremor, primary dystonia.

Multiple System Atrophy (MSA) Specific Criteria:

Inclusion Criteria:

1. Diagnosis of possible or probable multiple system atrophy.

2. Time since diagnosis < 3 years from baseline, with an expected survival of at least 3 years.

3. Stable treatment regimen for at least 1 month prior to dosing.

Exclusion Criteria:

1. Modified Unified Multiple System Atrophy Rating Scale (UMSARS) Part I score ≥ 14.

2. Presence of any condition that, in the investigators' judgment, affects thediagnosis or assessment of MSA.

Dementia with Lewy Bodies (DLB) Specific Criteria:

Inclusion Criteria:

1. Meets the revised consensus criteria for DLB (Fourth Consensus Report of the DLBConsortium, 2017).

2. Severity of motor symptoms must be ≤ stage 3 on the Hoehn and Yahr scale.

3. Clinical Dementia Rating (CDR) score ≤ 1.0.

4. Stable treatment regimen for at least 1 month prior to dosing.

Exclusion Criteria:

1. Patients currently diagnosed with any primary psychiatric disorder (e.g.,schizophrenia, bipolar disorder, or major depressive episode) according to DSM-V.

2. Patients with clinically significant or unstable systemic illness and exposure totoxicants within the past 5 years.

Frontotemporal Dementia (FTD) Specific Criteria:

Inclusion Criteria:

1. Meets the 2017 International Research Society (IRS) diagnostic criteria for FTD.

2. Clinical Dementia Rating (CDR) score ≤ 1.0.

3. Stable treatment regimen for at least 1 month prior to dosing.

Exclusion Criteria:

1. Diagnosis of severe central nervous system diseases other than FTD that may be thecause of the patient's FTD symptoms or may affect the study objectives.

Amyotrophic Lateral Sclerosis (ALS) Specific Criteria:

Inclusion Criteria:

1. Diagnosis of Amyotrophic Lateral Sclerosis (ALS) meeting the diagnostic criteria (Revised El Escorial Criteria, 2000 or Airlie House Criteria) at the level ofdefinite, probable, or laboratory-supported probable ALS.

2. Disease duration ≥ 6 months and ≤ 2 years (from the first occurrence of any ALSsymptom).

3. Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score: eachindividual item score ≥ 2 points (with the three respiratory items - Dyspnea,Orthopnea, and Respiratory Insufficiency - all scoring 4 points).

4. Stable treatment regimen for at least 1 month prior to dosing.

Exclusion Criteria:

1. Diagnosis of non-ALS patients based on clinical presentation and available auxiliaryclinical examinations (neurophysiology, MRI or other imaging techniques, laboratorytests, etc.).