Safety and Efficacy of Intrathecal NTF001 Injection in ALS (NTF-ALS)

Inclusion Criteria:

• Voluntarily participate in this study and sign the informed consent form.
• Agree to comply with study procedures and cooperate with all study-related assessments throughout the study.
• Male or female patients aged 18 to 65 years.
• Meet the diagnostic and exclusion criteria for amyotrophic lateral sclerosis according to the Chinese Expert Consensus on the Diagnosis and Treatment of Amyotrophic Lateral Sclerosis 2022 issued by the Neurology Branch of the Chinese Medical Association.
• Have a history of amyotrophic lateral sclerosis of no more than 5 years.

Exclusion Criteria:

• Mini-Mental State Examination (MMSE) score < 24.
• Patient Health Questionnaire-9 (PHQ-9) score ≥ 16.
• Abnormal liver or renal function, defined as AST or ALT > 1.5 × upper limit of normal (ULN), or serum creatinine (Cr) > 1.5 × ULN.
• Abnormal coagulation function or current use of anticoagulants.
• Positive infectious disease screening, including positive HBsAg or HBV-DNA, positive HCV-RNA, positive HIV test, or positive syphilis serology.
• Currently receiving antiviral treatment for hepatitis B or hepatitis C.
• Unstable or severe systemic diseases, including active tuberculosis, cardiovascular, respiratory, gastrointestinal, urinary, psychiatric or neurological disorders, such as epilepsy, hematological disorders, immune system diseases, or abnormal laboratory findings that, in the opinion of the investigator, make the participant unsuitable for this study.
• Current or previous history of malignant tumor.
• History of severe allergic reactions, allergy to contrast agents, or inability to undergo surgical anesthesia.
• Currently participating in another clinical trial, or participation in another clinical trial within 3 months before screening.
• Previous receipt of gene therapy before screening.
• Receipt of stem cell therapy within 6 months before screening.
• Use of other investigational drugs within 4 weeks before screening or within 5 half-lives of the investigational drug, whichever is longer, or use of any medication that, in the opinion of the investigator, may affect this study.
• Receipt of a live vaccine within 2 months before screening, or any vaccination within 30 days before screening.
• History of alcohol dependence or drug addiction, and inability to stop alcohol consumption as instructed during the study.
• Female participants who are pregnant or breastfeeding.
• Participants considered unsuitable for enrollment by the investigator.
• Patients requiring ventilator-assisted ventilation.
• Patients allergic to the investigational intervention.
• Patients with obvious signs of dementia.
• Patients with other psychiatric disorders that may affect disease assessment.
• Severely obese patients, defined as BMI > 35 kg/m².