This proposal will focus on (1) estimating oxidative capacity of specific muscle groups during exercise using near infrared spectroscopy and (2) describing body composition to better understand exercise capacity and mitochondrial function in ambulatory spinal muscular atrophy (SMA) patients and disease controls. It is a 6-month observational study including 14 ambulatory SMA patients, 14 ambulatory patients with mitochondrial myopathy, and 14 healthy controls.

Spinal Muscular Atrophy (SMA) is a progressive, recessively-inherited neuromuscular disease characterized by weakness and muscle atrophy due to the loss of spinal cord motor neurons. The results from this study would provide preliminary data, using non-invasive methods, on oxidative capacity in ambulatory SMA patients and disease controls to aid in the design of exercise intervention studies. Furthermore, this information would link previous laboratory and preclinical findings of mitochondrial depletion in SMA to the clinical condition and provide important information for future studies designed to improve oxidative capacity and fitness in SMA patients.

Inclusion Criteria:

1. One of the following categories:

   • Genetic confirmation of SMA with laboratory documentation of homozygous deletion of SMN1 exon 7;
   • Genetic confirmation of mitochondrial myopathy or evidence from muscle biopsy confirming the diagnosis; or
   • Healthy individuals.

2. Able to walk independently at least 25 meters, and able to tread a stationary cycle ergometer.

Exclusion Criteria:

1. Unable to walk 25 meters independently.
2. Use of investigational medications intended for the treatment of SMA within 30 days prior to study entry.
3. The presence of any contraindication to exercise according the ACSM criteria.

Patients with and without Spinraza treatment are eligible.

The study sample will include 14 ambulatory SMA patients, 14 ambulatory mitochondrial myopathy patients, and 14 healthy controls.