An Open-label Safety, Tolerability, and Dose-range Finding Study of ISIS SMNRx in Patients With Spinal Muscular Atrophy

Inclusion Criteria:

• Documented SMN1 homozygous gene deletion
• Clinical signs attributable to Spinal Muscular Atrophy
• Males and females 2 to 14 years of age at time of screening
• Able to complete all study procedures, measurements and visits and parent/patient has adequately supportive psychosocial circumstances, in the opinion of the investigator
• Estimated life expectancy > 2 years from Screening
• Meets age-appropriate institutional criteria for use of anesthesia/sedation, if use is planned for study procedure

Exclusion Criteria:

• Respiratory insufficiency defined by the need for invasive or non-invasive ventilation during a 24 hour period
• Presence of a gastric feeding tube
• Previous scoliosis surgery or scoliosis surgery planned during the duration of the study that would interfere with the LP injection procedure
• Hospitalization for surgery or pulmonary event within the last 2 months or planned during the study
• Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy
• History of brain or spinal cord disease that would interfere with lumbar puncture procedures or CSF circulation
• Presence of an implanted shunt for the draining of CSF or an implanted CNS catheter
• History of bacterial meningitis
• Clinically significant abnormalities in hematology or clinical chemistry parameters
• Treatment with another investigational drug, biological agent, or device within 1-month of Screening or 5 half-lives of study agent whichever is longer. Any history of gene therapy or cell transplantation
• Ongoing medical condition that would interfere with the conduct and assessments of the study. Examples are medical disability (e.g. wasting or cachexia, severe anemia, etc.) that would interfere with the assessment of safety or would compromised the ability of the patient to undergo study procedures