In this observational study, researchers are looking at the effects of spinal muscular atrophy (SMA) drugs on the muscles and nerve cells in patients with SMA.
Primary Objectives
* To evaluate the feasibility and reliability of performing MR functional imaging in exercising muscle in patients with SMA. * To evaluate patients with SMA types 2 and 3 at baseline and longitudinally at 6 and 12 months
Secondary Objectives
* To describe the MR functional bioenergetics response in muscles in five potential groups of patients with spinal muscular atrophy: untreated, actively treated with nusinersen (Spinraza®) or onasemnogene abeparvovec (Zolgensma®), actively treated with risdiplam (Evrysdi®), switching from Spinraza or Zolgensma to Evrysdi and initiating combination therapy of Spinraza or Zolgensma with Evrysdi . * To identify changes in motor function in patients with SMA types 2 and 3 who initiate treatment with risdiplam. * To obtain biomarkers in blood, urine, and muscle tissue to provide proof-of-concept support for risdiplam effect on skeletal muscle. * To obtain quality of life and disability data from participants in this study.
Genetic confirmation of SMA with homozygous deletion of SMN1 or compound heterozygous deletion/mutation of SMN1
Two, three, or four copies of SMN2
Age 5 to 20 years
Non-ambulatory participants: maximum function sitting or standing with support, HFMSE score at screening between 10 and 45 points.
Any chronic medical condition, planned surgery, or treatment with a medication which would impact safety or participation of the study at the investigator's discretion
Inability to perform reliably the motor function testing or the exercise testing in the MR scanner.
Fat fraction > 35% in calf or bicep at screening MRI
Need for routine non-invasive ventilation support.
Those who meet the Eligibility criteria and consent to enrollment on the study.
Case-only
Prospective
Not listed
Feasibility of performing MR functional imaging in SMA patients
MR functional imaging is considered feasible if ≥ 80% of MRI protocol eligible patients can complete 100% of imaging assessments at baseline and 6 months.
Reliability of performing MR functional imaging in SMA patients
MR functional imaging is considered reliable if the test-retest reliability is ≥ 0.80 for key imaging biomarkers.
Compare skeletal muscle oxidative phosphorylation bioenergetics in patients with SMA types 2 and 3 (phosphocreatine)
Real-time 31P MR spectroscopy and CrCEST MRI will be used to measure phosphocreatine within the muscles at rest, during an exercise protocol, and during post-exercise recovery to baseline. Both measure the recovery time in seconds.
Compare skeletal muscle oxidative phosphorylation bioenergetics in patients with SMA types 2 and 3 (creatine concentrations)
Real-time 31P MR spectroscopy and CrCEST MRI will be used to measure creatine concentrations within the muscles at rest, during an exercise protocol, and during post-exercise recovery to baseline. Both measure the recovery time in seconds.
Identify changes in motor function in non-ambulant patients and ambulant patients with SMA types 2 and 3
The Hammersmith Functional Motor Scale Expanded (HFMSE) has a score range from 0-66 with lower scores indicating poorer overall motor function.
Identify changes in motor function in non-ambulant patients with SMA types 2 and 3 - Revised Upper Limb Module
The Revised Upper Limb Module (RULM) has a score range 0-37 with lower scores indicating poorer upper limb motor function.
Identify changes in motor function in non-ambulant patients with SMA types 2 and 3 - Block and Box Test
The Block and Box Test (BBT) is a measure of gross manual dexterity and is scored by counting the number of blocks carried from one compartment to another. Higher scores are indicative of better manual dexterity.
Identify changes in motor function in ambulant patients with SMA types 2 and 3 - 6-Minute Walk
The 6-Minute Walk (6MW) Test measures how far someone can walk in six minutes, a higher score indicates better exercise tolerance score. A low score correlates with lower function.
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St. Jude Children's Research Hospital
Lead sponsor
Genentech, Inc.
Collaborator
