Exploring Nasal Drop Therapy With Small Extracellular Vesicles for ALS

Inclusion Criteria: * Age: 18-80 years, inclusion of both genders; * Disease duration: ≥6 months and ≤2 years (counted from the onset of any ALS symptoms); * Subjects must meet the El Escorial revised criteria (2000) for the diagnosis of ALS, with a diagnosis of Definite ALS, Probable ALS, Probable laboratory-supported ALS, or Possible ALS; * A score of ≥2 on each item of the revised ALS Functional Rating Scale (ALSFRS-R), with a score of 4 for items related to dyspnea, orthopnea, and respiratory insufficiency; * BMI: Between 18 and 30 kg/m²; * Subjects must have a baseline forced vital capacity percentage (%FVC) ≥70%; * Allowed concomitant treatments: Oral administration of riluzole/edaravone at standard doses for ≥30 days; regular intravenous edaravone with planned sequential oral treatment. During the trial and follow-up period, the dosage and type of concomitant medications must remain unchanged; * Subjects of childbearing potential must use appropriate and effective contraception from 2 weeks prior to trial enrollment until the end of the follow-up period; * The subject or legal representative must be able to sign an informed consent form and comply with the study requirements for medication administration and follow-up. Exclusion Criteria: * Diagnosed as non-ALS based on clinical presentation and available clinical examinations (e.g., neurophysiological tests, MRI, or other imaging, laboratory tests); * Abnormal nasal anatomy, nasal cavity damage, severe rhinitis, or nasal disease affecting the administration of the study drug; * Requires nasal insertion of a gastric tube; * Peripheral venous hemoglobin (HGB) \< 100 g/L, absolute neutrophil count (NEUT) \< 1.5×10\^9/L, platelet count (PLT) \< 100×10\^9/L, white blood cell count (WBC) \< 4.0×10\^9/L or ≥ 12×10\^9/L, serum albumin \< 30 g/L; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 3× the upper limit of normal (ULN); * Severe renal insufficiency: Glomerular Filtration Rate (GFR) \< 30 mL/min (Cockcroft-Gault formula), or other known severe renal diseases; * Positive for hepatitis B surface antigen, e antigen, e antibody, or core antibody combined with positive hepatitis B virus DNA; positive for hepatitis C virus antibody; positive syphilis serum antibody; or positive for HIV antibody; * History of acute myocardial infarction or interventional treatment within the last 6 months, or heart failure (classified as NYHA III-IV); * Presence of severe localized or systemic infection, immunodeficiency, or currently taking immunosuppressants; * Concurrent severe systemic diseases such as immunodeficiency diseases, coagulation disorders, or malignancies; * Vaccination within 1 month prior to the first administration or during the study until the end of follow-up; * Known allergy to the drugs used in this study or similar drugs; * Participation in another study and administration of an investigational product within the last 3 months; * Contraindications to MRI (e.g., presence of metal implants) or inability to tolerate MRI (e.g., claustrophobia); * Pregnant or breastfeeding women, or women of childbearing potential who cannot or are unwilling to use appropriate contraception; * Unwillingness or inability to comply with the procedures required by the protocol; * Any other conditions deemed unsuitable for inclusion by the investigators.