Please select the eligibility criteria that correspond to the clinical trial below.
Title: Evaluation of the Muscle Strength and Motor Ability in Children With Spinal Muscle Atrophy Type II and III Treated With Valproic Acid
Brief Summary: The purpose of this study is to determine if the treatment with valproic acid can increase the muscle strength and motor ability of children with spinal muscular atrophy.


Options:
A: Inclusion Criteria:

* Regularly attended at the Out-patient Service of Neuromuscular Disorders and Child Neurology of our Institution;
* More than 2 years olf and had a molecular analysis of Spinal Muscular Atrophy;

Exclusion Criteria:

* Had been submitted into a surgery recently;
* Did not come to the evaluation and medical sessions:
* Did not take the medication correctly
B: Inclusion Criteria:

Cohort 1

* Confirmed genetic diagnosis of 5q SMA
* SMA 2 or non-ambulatory SMA 3: all subjects must be able to sit independently for at least 3 seconds without support
* Age 2 to 8 years at time of enrollment

Cohort 2

* Confirmed genetic diagnosis of 5q SMA
* SMA subjects (SMA types 2 or 3) who can stand independently without braces or other support for up to 2 seconds, or walk independently
* Age 3 to 17 years at time of study enrollment

Exclusion Criteria:

Cohort 1

* Need for BiPAP support \> 12 hours per day
* Spinal rod or fixation for scoliosis or anticipated need within six months of enrollment
* Inability to meet study visit requirements or cooperate reliably with functional testing
* Coexisting medical conditions that contraindicate travel, testing or study medications
* Use of medications or supplements which interfere with valproic acid or carnitine metabolism within 3 months of study enrollment.
* Current use of either VPA or carnitine. If study subject is taking VPA or carnitine then patient must go through a washout period of 12 weeks before enrollment into the study
* Body Mass Index \> 90th % for age

Cohort 2

* Spinal rod or fixation for scoliosis or anticipated need within six months of enrollment
* Inability to meet study visit requirements or cooperate with functional testing
* Transaminases, amylase or lipase \> 3.0 x normal values, WBC \< 3.0 or neutropenia \< 1.0, platelets \< 100 K, or hematocrit \< 30 persisting over a 30 day period.
* Coexisting medical conditions that contraindicate travel, testing or study medications
* Use of medications or supplements which interfere with valproic acid or carnitine metabolism within 3 months of study enrollment.
* Current use of either VPA or carnitine. If study subject is taking VPA or carnitine then patient must be go through a washout period of 12 weeks before enrollment in the study.
* Body Mass Index \> 90th % for age
* Pregnant women/girls, or those intending to try to become pregnant during the course of the study.
C: Key Inclusion Criteria:

* Be born (gestational age) between 37 and 42 weeks
* Be medically diagnosed with spinal muscular atrophy (SMA)
* Have Survival Motor Neuron2 (SMN2) Copy number = 2
* Body weight equal to or greater than 3rd percentile for age using appropriate country-specific guidelines
* Be able to follow all study procedures
* Reside within approximately 9 hours ground-travel distance from a participating study center, for the duration of the study

Key Exclusion Criteria:

* Hypoxemia (oxygen \[O2\] saturation awake less than 96% or O2 saturation asleep less than 96%, without ventilation support) during screening evaluation
* Clinically significant abnormalities in hematology or clinical chemistry parameters or Electrocardiogram (ECG), as assessed by the Site Investigator, at the Screening visit that would render the participant unsuitable for participation in the study
* Participant's parent or legal guardian is not willing to meet standard of care guidelines (including vaccinations and respiratory syncytial virus prophylaxis if available), nor provide nutritional and respiratory support throughout the study

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
D: Inclusion Criteria:

* Six or nine months of age and younger (depending on cohort) on day of vector infusion with Type 1 SMA as defined by the following features:

  * Diagnosis of SMA based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and 2 copies of SMN2.
  * Onset of disease at birth up to 6 months of age.
  * Hypotonia by clinical evaluation with delay in motor skills, poor head control, round shoulder posture and hypermobility of joints.

Exclusion Criteria:

* Active viral infection (includes HIV or serology positive for hepatitis B or C)
* Use of invasive ventilatory support (tracheotomy with positive pressure)\* or pulse oximetry \<95% saturation.
* Patients may be put on non-invasive ventilator support (BiPAP) for less than 16 hours a day at the discretion of their physician or research staff.
* Concomitant illness that in the opinion of the PI creates unnecessary risks for gene transfer
* Concomitant use of any of the following drugs: drugs for treatment of myopathy or neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive therapy or immunosuppressive therapy within 3 months of starting the trial (e.g. corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab)
* Patients with Anti-AAV9 antibody titers \>1:50 as determined by ELISA binding immunoassay.
* Abnormal laboratory values considered clinically significant (GGT \> 3XULN, bilirubin ≥ 3.0 mg/dL , creatinine ≥ 1.8 mg/dL, Hgb \< 8 or \> 18 g/Dl; WBC \> 20,000 per cmm) Participation in a recent SMA treatment clinical trial that in the opinion of the PI creates unnecessary risks for gene transfer.
* Family does not want to disclose patient's study participation with primary care physician and other medical providers.
* Patient with signs of aspiration based on a swallowing test and unwilling to use an alternative method to oral feeding.
* Patients with a single base substitution in SMN2 (c.859G\>C in exon 7) will be excluded based on predicted mild phenotype.

Answer: A