A Study to Evaluate the Safety and Efficacy of Zilganersen (ION373) in Patients With Alexander Disease (AxD)

Key Inclusion Criteria:

1. Clinical phenotype and brain imaging consistent with a diagnosis of Alexanderdisease

2. Documented genetic mutation in the GFAP gene

3. Aged ≥ 2 to 65 years old at the time of informed consent

4. Able and willing to meet all study requirements, including travel to Study Center,procedures, measurements and visits

5. Patients < 18 years old at Screening must have a trial partner (parent, caregiver orother)

Key Exclusion Criteria:

1. Clinically significant abnormalities in medical history or physical examination

2. Any clinically significant laboratory abnormalities that would render a patientunsuitable for inclusion

3. Any contraindication or unwillingness to undergo MRI

4. Treatment with another investigational drug, biological agent, or device within 1month of Screening, or 5 half-lives of investigational agent, whichever is longer;concurrent participation in any other clinical study (including observational andnon-interventional studies)

5. Previous treatment with an oligonucleotide (including small interfering ribonucleicacid [siRNA]) within 4 months of Screening if single dose received, or within 12months of Screening if multiple doses received. This exclusion does not apply tovaccines (both messenger ribonucleic acid [mRNA] and viral vector vaccines).

6. History of gene therapy or cell transplantation or any other experimental brainsurgery [ROW]

7. Obstructive hydrocephalus

8. Presence of a functional ventriculoperitoneal shunt for the drainage ofcerebrospinal fluid (CSF) or an implanted central nervous system (CNS) catheter

9. Known brain or spinal disease that would interfere with the lumbar puncture (LP)process, CSF circulation or safety assessment.

10. Hospitalization for any major medical or surgical procedure involving generalanesthesia within 12 weeks prior to Screening or planned during the study

11. Have any other conditions, which, in the opinion of the Investigator would make thepatient unsuitable for inclusion, or could interfere with the patient participatingin or completing the study