Spinraza in Adult Spinal Muscular Atrophy

Inclusion Criteria:

1. Ability to understand the purpose and risks of the study and provide signed anddated informed consent and authorization to use protected health information (PHI)in accordance with national and local subject privacy regulations.

2. Males and females with SMA type II or type III, aged 18 to 70 years at the time ofenrollment.

3. Genetic documentation of 5Q SMA homozygous gene deletion, mutation, or compoundheterozygote.

4. Are treatment naïve for SPINRAZA® (nusinersen).

5. Have been prescribed SPINRAZA® (nusinersen) by the treating physician as part oftheir clinical care for SMA following the FDA approved prescribing informationguidelines as follows: dose level (12 mg), dosing schedule (3 loading dosesadministered at 14-day intervals, and the fourth loading dose administered 30 daysafter the third dose and subsequent maintenance doses administered every 4 months)and safety lab monitoring (CBC, PT, INR, PTT, UA) done prior to each doseadministration.

6. Believed to be able to complete all study procedures, measurements and visits.

7. Estimated life expectancy at least 30 months from first dosing, in the opinion ofthe Investigator.

8. Revised upper limb module (RULM) score ≥ 4 (more than marginal upper extremityfunction/strength.

9. Must meet either Group 1 or Group 2 criteria.

For Group 1 subjects:

1. May be ambulatory or non-ambulatory (defined as being wheelchair reliant at least 75% of time and unable to walk at least 10 meters without assistance).

2. RULM score of 4-34, inclusive.

For Group 2 subjects:

1. Ability to walk at least 10 meters without assistance (i.e., four point walkingaid).

2. Be free of major orthopedic deformities that limit ambulation.

3. An ambulatory subject can qualify for both Group 1 and Group 2 if the RULM score is ≤ 34.

Exclusion Criteria:

1. Revised upper limb score ≤ 3.

2. Respiratory insufficiency, defined by the medical necessity for invasive ornoninvasive ventilation for >16 hours during a 24-hour period, at screening.

3. Hospitalization for major medical event including: surgery (i.e., scoliosis surgery,other surgery), cardiac event, pulmonary event, or other major medical problemwithin 2 months of screening or planned major surgical procedure likely to impactthe clinical assessments during the duration of the study. Outpatient surgicalprocedure (i.e., placement of feeding tube) is not considered an exclusionary majormedical event.

4. Presence of a symptomatic severe active infection or illness during the screeningperiod that is likely to impact the performance on the clinical assessments.

5. Prior exposure to SPINRAZA® (nusinersen).

6. Prior disorder, injury (e.g., upper or lower limb fracture) or surgical procedurewhich impacts the subject's ability to perform any of the outcome measure testingrequired in the protocol and from which the subject has not fully recovered orachieved a stable baseline.

7. Treatment with an investigational drug (e.g., oral albuterol/salbutamol, riluzole,carnitine, creatine, sodium phenylbutyrate, etc.), biological agent, or devicewithin 1-month of Screening or 5 half-lives of study agent, whichever is longer.Patients using intrathecal drug delivery devices, including investigational deviceswith an active IDE designation in the United States, may be eligible but requireStudy PI approval prior to enrollment.

8. Any history of exposure to gene therapy, antisense oligonucleotide therapy, or celltransplantation that was intended for the treatment of SMA.

9. Ongoing medical condition that according to the Clinical Center Investigator wouldinterfere with the conduct and assessments of the study. Examples are medicaldisability (e.g., wasting or cachexia, severe anemia, etc.) that would interferewith the assessment of safety or would compromise the ability of the subject toundergo study procedures.

For Cohort 2 Inclusion criteria

1. Ability to understand the purpose and risks of the study and provide signed anddated informed consent and authorization to use protected health information (PHI)in accordance with national and local subject privacy regulations.

2. Males and females with SMA type II or type III, aged 18 to 70 years at the time ofenrollment.

3. Genetic documentation of 5Q SMA homozygous gene deletion, mutation, or compoundheterozygote.

4. Believed to be able to complete the structured interview.

Cohort 2 Exclusion Criteria

1. Ongoing medical condition that according to the Clinical Center Investigator wouldinterfere with the conduct and assessments of the study.