Key Inclusion Criteria:  Clinical phenotype and brain imaging consistent with a diagnosis of Alexander disease Documented genetic mutation in the GFAP gene Aged ≥ 2 to 65 years old at the time of informed consent Able and willing to meet all study requirements, including travel to Study Center, procedures, measurements and visits Patients < 18 years old at Screening must have a trial partner (parent, caregiver or other)  Key Exclusion Criteria:  Clinically significant abnormalities in medical history or physical examination Any clinically significant laboratory abnormalities that would render a patient unsuitable for inclusion Any contraindication or unwillingness to undergo MRI Treatment with another investigational drug, biological agent, or device within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer; concurrent participation in any other clinical study (including observational and non-interventional studies) Previous treatment with an oligonucleotide (including small interfering ribonucleic acid [siRNA]) within 4 months of Screening if single dose received, or within 12 months of Screening if multiple doses received History of gene therapy or cell transplantation or any other experimental brain surgery Obstructive hydrocephalus Presence of a functional ventriculoperitoneal shunt for the drainage of CSF or an implanted CNS catheter Known brain or spinal disease that would interfere with the LP process, CSF circulation or safety assessment. Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks prior to Screening or planned during the study Have any other conditions, which, in the opinion of the Investigator would make the patient unsuitable for inclusion, or could interfere with the patient participating in or completing the study