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

Prior treatment

• Subjects who have received allogeneic mesenchymal progenitor cell therapy or its derived small extracellular vesicles.
• Subjects with abnormal nasal anatomy, nasal damage, severe rhinitis, or other nasal conditions that may affect the administration of the investigational product.
• Contraindications to MRI examination (e.g., metal implants) or inability to tolerate MRI (e.g., claustrophobia).
• Vaccination within 1 month prior to the first dose or planned during the period from enrollment until the end of follow-up.
• Participation in other clinical drug studies within the past 30 days.
• 1\. Parkinsonism other than PD, including but not limited to progressive supranuclear palsy (PSP), multiple system atrophy (MSA), vascular parkinsonism, drug-induced parkinsonism, essential tremor, primary dystonia.

Other illness

• Suffering from other uncontrolled diseases that may interfere with the study results, including but not limited to severe local infection, systemic infection, or immunodeficiency.
• Combined with malignant tumors, hematological malignancies, or other serious systemic diseases.
• Clinically significant history of allergic reactions, especially drug allergic reactions.
• HBsAg positive, or HBcAb positive with HBV DNA positive, hepatitis C virus (HCV) antibody positive, peripheral blood HCV RNA positive, HIV antibody positive; CMV DNA positive, syphilis serology positive.
• Any condition that, in the investigator's judgment, may compromise the subject's ability to understand and/or comply with the study procedures and/or follow-up.
  • Alzheimer's Disease (AD) Specific Criteria:
• Major history of significant brain injury with persistent neurological impairment (with or without) or known structural brain abnormalities.
• 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 systemic illnesses (e.g., hepatic encephalopathy, pulmonary encephalopathy), intracranial space-occupying lesions (e.g., subdural hematoma, brain tumor), endocrine disorders (e.g., thyroid disease, parathyroid disease), vitamin B12 or folate deficiency, or any other known causes.
  • Parkinson's Disease (PD) Specific Criteria:
• Presence of any condition that, in the investigators' judgment, affects the diagnosis or assessment of MSA.
  • Dementia with Lewy Bodies (DLB) Specific Criteria:
• Patients currently diagnosed with any primary psychiatric disorder (e.g., schizophrenia, bipolar disorder, or major depressive episode) according to DSM-V.
• Patients with clinically significant or unstable systemic illness and exposure to toxicants within the past 5 years.
  • Frontotemporal Dementia (FTD) Specific Criteria:
• 1\. Diagnosis of severe central nervous system diseases other than FTD that may be the cause of the patient's FTD symptoms or may affect the study objectives.

Lab values

• Severe renal insufficiency: creatinine clearance (CrCl) \< 30 mL/min (calculated by Cockcroft-Gault formula), or other known severe renal diseases.
• 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) and aspartate aminotransferase (AST) ≥ 3 × upper limit of normal (ULN).
• 1\. Diagnosis of non-ALS patients based on clinical presentation and available auxiliary clinical examinations (neurophysiology, MRI or other imaging techniques, laboratory tests, etc.).

Other

• Subjects requiring nasogastric tube insertion.
• Women of childbearing potential not intending to use effective contraception during the trial or within 90 days after the last dose and with a positive pregnancy test record; pregnant or lactating women; men who are sexually active during the trial or within 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 last dose.
• Multiple System Atrophy (MSA) Specific Criteria:
• Modified Unified Multiple System Atrophy Rating Scale (UMSARS) Part I score ≥ 14.
• Amyotrophic Lateral Sclerosis (ALS) Specific Criteria:

• Age 18-80 years (inclusive), any gender.
• Subjects or their legal guardians voluntarily sign a written informed consent form and are able to comply with the study requirements for dosing and follow-up.
• Probable AD as defined by the 2011 National Institute on Aging-Alzheimer's Association (NIA-AA) criteria.
• Clinical Dementia Rating (CDR) score ≤ 1.0.
• Subjects have an identified, reliable caregiver.
• Stable treatment regimen for at least 1 month prior to dosing.
• Diagnosis of PD according to the 2015 Movement Disorder Society (MDS) clinical diagnostic criteria for PD.
• Hoehn and Yahr stage ≤ 3.
• Stable treatment regimen for at least 1 month prior to dosing.
• Diagnosis of possible or probable multiple system atrophy.
• Time since diagnosis \< 3 years from baseline, with an expected survival of at least 3 years.
• Stable treatment regimen for at least 1 month prior to dosing.
• Meets the revised consensus criteria for DLB (Fourth Consensus Report of the DLB Consortium, 2017).
• Severity of motor symptoms must be ≤ stage 3 on the Hoehn and Yahr scale.
• Clinical Dementia Rating (CDR) score ≤ 1.0.
• Stable treatment regimen for at least 1 month prior to dosing.
• Meets the 2017 International Research Society (IRS) diagnostic criteria for FTD.
• Clinical Dementia Rating (CDR) score ≤ 1.0.
• Stable treatment regimen for at least 1 month prior to dosing.
• Diagnosis of Amyotrophic Lateral Sclerosis (ALS) meeting the diagnostic criteria (Revised El Escorial Criteria, 2000 or Airlie House Criteria) at the level of definite, probable, or laboratory-supported probable ALS.
• Disease duration ≥ 6 months and ≤ 2 years (from the first occurrence of any ALS symptom).
• Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score: each individual item score ≥ 2 points (with the three respiratory items - Dyspnea, Orthopnea, and Respiratory Insufficiency - all scoring 4 points).
• Stable treatment regimen for at least 1 month prior to dosing.

Criteria the registry did not label

• General Criteria: