• Safety (including Tolerability), measured through safety labs and parent reports [ Time Frame: -4 wks, 0, 2 wks, 3 mo, 6 mo, 9 mo, 12 mo for safety labs; throughout for AEs ] [ Designated as safety issue: Yes ]
• Efficacy, measured through motor function assessments [ Time Frame: -4wks, 0, 3 mo, 6 mo, 12 mo ] [ Designated as safety issue: Yes ]

• Cohort 1:
• 1.Safety
• 2.Functional Status/Strength as assessed via Modified Hammersmith Functional Motor Scale (MHFMS)
• Cohort 2:
• 1.Safety labs:
• 2.Project Cure Functional Motor Scale for SMA
• 3.Myometry > 5 yrs (CITEC) right-sided grip, elbow flexion, knee extension

• Quantitative assessment of SMN mRNA from blood samples [ Time Frame: -4wks or 0, 3 mo, 6 mo, 12 mo ] [ Designated as safety issue: No ]
• Peds QL™ assessment: parental version (all), child versions (> 5yrs) [ Time Frame: -4wks, 0, 3mo, 6mo, 12mo ] [ Designated as safety issue: Yes ]
• Max CMAP amplitude/area [ Time Frame: -4wks, 0, 3mo, 6mo, 12mo ] [ Designated as safety issue: Yes ]
• Ulnar MUNE [ Time Frame: -4 wks, 0, 3 mo, 6 mo, 12 mo ] [ Designated as safety issue: Yes ]
• Growth and vital sign parameters [ Time Frame: -4 wks, 0, 3mo, 6mo, 12mo ] [ Designated as safety issue: Yes ]
• Nutritional Status [ Time Frame: -4 wks, 0, 3mo, 6mo, 12mo ] [ Designated as safety issue: Yes ]
• DEXA [ Time Frame: 0, 6mo, 12mo ] [ Designated as safety issue: Yes ]
• Pulmonary Function for pts 5 years+ [ Time Frame: 0, 3mo, 6mo, 12mo ] [ Designated as safety issue: Yes ]

• Cohorts 1 & 2
• 1.Pulmonary Function Testing:
• 2.Quantitative assessment of SMN mRNA from blood samples
• 3.Peds QL™ assessment: parental version (all), child versions (> 5yrs)
• 4.Max CMAP amplitude/area
• 5.Ulnar MUNE
• 6.Growth and vital sign parameters
• 7.Nutritional Status

This is a multi-center trial to assess safety and efficacy of a combined regimen of oral valproic acid (VPA) and carnitine in patients with Spinal Muscular Atrophy (SMA) 2 to 17 years of age. Cohort 1 is a double-blind placebo-controlled randomized intention to treat protocol for SMA "sitters" 2 - 8 years of age. Cohort 2 is an open label protocol for SMA "standers and walkers" 3 - 17 years of age to explore responsiveness of efficacy outcomes. Outcome measures will include blood chemistries, functional testing, pulmonary function testing, electrophysiological evaluations, PedsQL quality of life assessment, quantitative assessments of survival motor neuron (SMN) mRNA from blood samples, growth and vital sign parameters. Six centers will enroll a total of 90 patients.

This is a multi-center phase II trial of a combined regimen of oral valproic acid (VPA) and carnitine in patients with Spinal Muscular Atrophy (SMA) 2 to 17 years of age. Cohort 1 is a double-blind placebo-controlled randomized intention to treat protocol for SMA "sitters" 2 - 8 years of age. Subjects will undergo two baseline assessments over 4 to 6 week period, then will be randomized to treatment or placebo for the next six months. All subjects will then be placed on active treatment for the subsequent six month period. Cohort 2 is an open label protocol for SMA "standers and walkers" 3 - 17 years of age to explore responsiveness of efficacy outcomes. Subjects will undergo two baseline assessments over a four to six week period, followed by one year active treatment with VPA and carnitine. Outcome measures are performed every 3 to 6 months, and include blood chemistries, functional testing, pulmonary function testing, electrophysiological evaluations, PedsQL quality of life assessment, quantitative assessments of survival motor neuron (SMN) mRNA from blood samples, growth and vital sign parameters. Six centers will enroll a total of 90 patients.

• Placebo Comparator: For six months, Cohort 1 pts are randomized into placebo or treatment. After 6 months, all pts are on treatment. Cohort 2 pts are on open-label treatment throughout
• Active Comparator: For six months, Cohort 1 pts are randomized into placebo or treatment. After 6 months, all pts are on treatment. Cohort 2 pts are on open-label treatment throughout.
• Experimental: For six months, Cohort 1 pts are randomized into placebo or treatment. After 6 months, all pts are on treatment. Cohort 2 pts are on open-label treatment throughout.

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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.

• Families of Spinal Muscular Atrophy
• Sigma Tau Pharmaceuticals, Inc.
• Abbott