Study on the Safety and Efficacy of RAG-21 in the Treatment of Amyotrophic Lateral Sclerosis Patients With FUS Gene Mutations

Inclusion criteria

• Age 18-75 years, gender unlimited.
• Clearly identify amyotrophic lateral sclerosis (ALS) patients with FUS gene mutations (known FUS mutation sites and reported disease progression).
• Forced vital capacity (FVC) during screening period ≥ 50% of expected lung capacity.
• ALS patients diagnosed according to the Gold Coast criteria (2020) with limb-onset weakness.
• The patient or their legal representative clearly understands and voluntarily participates in the study and signs an informed consent form.
• The subjects (including male subjects) have no family planning throughout the entire study and within 3 months after, voluntarily take effective contraceptive measures and without any plans to donate sperm or ovum.

Exclusion criteria

• FUS mutation sites located within nucleotides 928-970 (calculated from the translation of FUS protein).
• Patients who have previously received or are currently receiving Ulefnersen treatment.
• Human immunodeficiency virus (HIV) test positive or positive test history.
• Patients with active hepatitis C or hepatitis B infection.
• Other experimental drugs used within one month or within five drug half-lives.
• Lumbar diseases and deformities.
• ALS with bulbar-onset symptoms, or suffering from other diseases known to be related to motor neuron dysfunction, which may confuse or blur the diagnosis of ALS.
• Other psychiatric disorders diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (DSM-V) diagnostic criteria, or obvious suicidal intentions.
• Combined with severe liver dysfunction, renal dysfunction, or severe heart dysfunction (severe liver dysfunction refers to alanine aminotransferase (ALT) value ≥ 2.0 times the upper limit of normal value or aspartate aminotransferase (AST) value ≥ 2.0 times the upper limit of normal value; severe renal dysfunction refers to creatinine (CRE) ≥ 1.5 times the upper limit of normal value or estimated glomerular filtration rate (eGFR) < 40mL/min/1.73m^2; severe heart dysfunction refers to New York College of Cardiology (NYHA) 3-4 levels).
• Permanent and sustained dependence on ventilator assisted ventilation.
• History of combined alcohol and drug abuse.
• Pregnant, lactating, or potentially pregnant patients, as well as those planning to conceive.
• Patients participating in other clinical trials or applying other biologics, drugs, or devices under study.
• Patients who have received any vaccination within 28 days.
• Those who can't complete follow-up due to other reasons.