An Open-label Safety and Tolerability Study of ISIS SMNRx in Patients With Spinal Muscular Atrophy Who Previously Participated in ISIS 396443-CS1

This study will test the safety, tolerability, and pharmacokinetics of a single dose of
ISIS-SMNRx administered as a single intrathecal injection. The single dose will be studied
in patients who previously participated in ISIS 396443-CS1, and all patients will receive
active drug.

Inclusion Criteria:

- Clinical signs attributable to Spinal Muscular Atrophy

- Satisfactory completion of dosing and all study visits in ISIS 396443-CS1 with an
acceptable safety profile, per Investigator judgement.

- 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:

- Have any new or worsening of existing condition which in the opinion of the
Investigator would make the subject unsuitable for enrollment, or could interfere
with the subject participating in or completing the study.

- Dosing in ISIS 396443-CS1 within 270 days (9 months) of screening, or longer ago than
450 days (15 months)

- Dosing in ISIS 396443-CS2

- Hospitalization for surgery (i.e. scoliosis surgery) or pulmonary event within 2
months of screening or planned during the duration of the study

- Presence of an untreated or inadequately treated active infection requiring systemic
antiviral or antimicrobial therapy any time during the screening period

- Clinically significant abnormalities in hematology or clinical chemistry parameters

- Treatment with investigational drug, biological agent, or device within 1-month of
Screening or 5 half-lives of study agent, whichever is longer. Treatment with
valproate or hydroxyurea within 1 months of screening. Any history of gene therapy or
cell transplantation