This study is testing a drug called **Tofersen** on patients with a type of ALS (a disease that affects the nerve cells in the brain and spinal cord) that is not due to a mutation in the SOD1 gene. Tofersen is already approved for treating ALS with the SOD1 gene mutation. The study wants to see if Tofersen is safe and if it helps lower a protein called neurofilament light chain (NfL) in the blood and spinal fluid, which might show it is working against ALS. Participants will be given Tofersen through a lumbar puncture (a procedure to collect fluid from the spine) for 24 weeks. They will have to visit the study site for the procedure at specific weeks and have two follow-up visits afterward. Participants will also complete tests and questionnaires to check their health and quality of life. **Key Points**: - The study lasts 32 weeks with 8 dosing visits and 2 follow-up visits. - Participants need to be 18 or older with non-SOD1 ALS and meet other health criteria. - Participants must agree to use contraception during and for a period after the study. **Note:** This study is not suitable for those with certain health conditions or who are already in another trial.