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 the leg muscles in four potential groups of patients with spinal muscular atrophy: untreated, actively treated with nusinersen (Spinraza®) or onasemnogene abeparvovec (Zolgensma®), actively treated with risdiplam (Evrysdi®), and switching from Spinraza or Zolgensma to 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, never walked independently, still able to sit independently for 5 seconds at screening, with active ankle plantar flexion strength of at least 3 N with hand-held myometry and capable of performing repetitive maximal plantar flexion effort for 120 seconds. HFMSE score at screening between 10 and 45 points.
Labs at screening that are abnormal and identified as clinically significant by the PI: CBC, and CMP, liver function tests (over twice the upper limit of normal), PT/PTT, urine protein of 2+ or greater.
Inability to perform reliably the motor function testing or the exercise testing in the MR scanner.
Treatment with a possible SMA-enhancing or mitochondrial-enhancing medication, unless discontinued within 3 months prior to screening: oral albuterol, hydroxyurea, phenylbutryate, valproic acid, creatine, l-carnitine, or other mitochondrial type supplement (riboflavin, lipoic acid, etc.). A daily multivitamin and Vitamin D supplement and intermittent inhaled albuterol are permitted if the dosage is unchanged during the study.
Need for routine non-invasive ventilation support.
St. Jude Children's Research Hospital
Lead sponsor
Genentech, Inc.
Collaborator