Tofersen in Non-SOD1 ALS

Exclusion Criteria

• •Treatment with another investigational drug (including investigational drugs for ALS through compassionate use or expanded access programs), biological agent, or device within 1 month or 5 half-lives of study agent, whichever is longer. Specifically, no prior treatment with small interfering RNA, stem cell therapy, or gene therapy is allowed.
• •Current enrollment in any other interventional study.
• •History of drug abuse or alcoholism within ≤ 6 months of study enrollment that would limit participation in the study, as determined by the Investigator.
• •Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the screening period.
• •Ongoing medical condition (e.g., wasting or cachexia, severe anemia) that according to the Investigator would interfere with the conduct or assessments of the study.
• •History of confounding neuromuscular or neurological disorder that is expected to have a progressive (i.e., worsening) course during the study, and/or is expected to be associated with elevations in neurofilament, in the opinion of the Investigator.
• •Female participants who are pregnant or currently breastfeeding.
• •Significant cognitive impairment, clinical dementia, or unstable psychiatric illness, including psychosis, suicidal ideation, suicide attempt, or untreated major depression ≤ 90 days, as determined by the Investigator.
• •History of allergies to a broad range of anesthetics.
• •Tracheostomy.
• •Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that is not managed optimally could place a participant at an increased risk for intraoperative or postoperative bleeding. These could include, but are not limited to, anatomical factors at or near the LP site (e.g., vascular abnormalities, neoplasms, or other abnormalities) and underlying disorders of the coagulation cascade, platelet function, or platelet count (e.g., hemophilia, Von Willebrand's disease, liver disease).
• •Anticipated need, in the opinion of the Investigator, for administration of any antiplatelet or anticoagulant medication that cannot be safely held before and/or after an LP procedure according to local or institutional guidelines and/or Investigator determination.
• •Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter.
• •Clinically significant abnormalities in hematology or clinical chemistry parameters, as determined by the Investigator, which would render the participant unsuitable for enrollment.
• •Inability to comply with study requirements.
• •Other unspecified reasons that, in the opinion of the Investigator, make the participant unsuitable for enrollment.