Exploring the Physiologic, Pharmacodynamic, and Clinical Responses of Skeletal Muscle in Patients With Spinal Muscular Atrophy Treated With SMN-Directed Therapies

Ki vehet részt

• 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
• Ambulatory participants: minimum function of independent walking, able to walk unassisted a minimum of 100 meters at screening, HFMSE score at screening between 40 and 66
• SMN-directed therapy inclusion:; Current Evrysdi prescription (Group 1); Must have Evrysdi prescription through their treating physician; If initiating combined therapy using Evrysdi with Spinraza or Zolgensma, must have not started Evrysdi treatment OR; Current Spinraza or Zolgensma prescription (Group 2); For patients on Spinraza, must have been taking Spinraza for at least 12 months at screening (4 loading and 2 maintenance doses) and following the FDA-recommended dosing schedule; For patients on Zolgensma, must have been dosed at least one year prior to screening; Must have Spinraza or Zolgensma prescription through their treating physician OR; Changing from Spinraza or Zolgensma to Evrysdi (Group 3); For patients on Spinraza, must have been taking Spinraza for at least 12 months at screening (4 loading and 2 maintenance doses) and following the FDA-recommended dosing schedule; For patients on Zolgensma, must have been dosed at least one year prior to screening; Must have voluntarily decided to switch therapies based on discussion with their treating physician; Must have Evrysdi prescription through their treating physician but have not yet initiated treatment OR; Have never received any SMN-directed therapies (Group 4)

Ki nem vehet részt

• 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
• Any ferrous metal implants (e.g., spinal rods) that preclude testing in a MR scanner
• 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
• Non-oral nutritional support, e.g., gastrostomy tube feeding