A Study Evaluating the Safety and Tolerability of QRL-201 in ALS

Inclusion Criteria (Double-Blind Periods): * Male or female participants aged 18 to 80 years diagnosed with ALS * ALS symptom onset within 24 months of Screening * Slow vital capacity \>50% * Clinical or electrodiagnostic evidence of lower motor neuron involvement * Not pregnant and not nursing * Willing and able to practice effective contraception * Able to tolerate lumbar puncture * If on approved therapies for the treatment of ALS during the course of the study, must be on a stable dose (at the Sponsor's discretion) Exclusion Criteria (Double Blind Periods): * Pathogenic variant, likely pathogenic variant, or variant of uncertain significance in the superoxide dismutase 1 (SOD1) and/or fused in sarcoma (FUS) genes * Currently enrolled in any other clinical study involving either an investigational product (IP) or off-label use of a drug or device * Prior exposure to stem cell or gene therapy products * Any contraindication to intrathecal drug administration * Abnormal laboratory values deemed clinically significant by the Investigator * Significant infection or known inflammatory process * Any sign and/or history of neurological conditions and other neuromuscular disorders that could affect the electrophysiological recordings. * An EEG that shows signs of abnormal electrical activity (e.g., epilepsy) Inclusion Criteria (Open-Label Extended Dosing Period): * Male or female participants in the sporadic ALS and C9orf72 ALS Cohorts of QRL-201-01 who have completed through at least Day 253 of safety follow up in the double-blind study period OR have completed Cohort 1 of Cohort 2 * Not pregnant and not nursing * Willing and able to practice effective contraception * Can visit study site for required visits * Able to tolerate lumbar puncture * If on approved therapies for the treatment of ALS during the course of the study, must be on a stable dose (at the Sponsor's discretion) Exclusion Criteria (Open-Label Extended Dosing Period): * Currently enrolled in any other clinical study involving either an investigational product (IP) or off label use of a drug or device * Off-label use of drugs or devices that are being used as disease-modifying therapies in ALS * Participated in another clinical study within 30 days, or 5 half-lives of the previous investigational product, whichever is greater, prior to the first dose * Prior exposure to stem cell or gene therapy products * Is not suitable for inclusion in the Open-Label Extended Dosing period of the study, in the opinion of the Investigator * An EEG that shows signs of abnormal electrical activity (NOTE: Cohort 1 and Cohort 2 participants only)