Pilot Study Exploring the Physiologic, Pharmacodynamic, and Clinical Responses of Skeletal Muscle in Patients With Spinal Muscular Atrophy Treated With SMN-Directed Therapies
St. Jude Children's Research Hospital
Summary
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.
Description
This is an observational study to demonstrate the feasibility of performing MR functional imaging in exercising muscle in patients with SMA. The participants will be prescribed medication by their treating physician, they will not receive any drug as part of this study. Participants participating in the ML43225 study, will be put into one of four groups depending on their type of SMA and the drugs they may or may not be taking. They will be asked to come to clinic 3 times over one year. Each visit will include magnetic resonance (MR) studies, a muscle ultrasound, a nerve test, muscle function…
Eligibility
- Age range
- 5–20 years
- Sex
- All
- Healthy volunteers
- Not specified
Inclusion Criteria: * 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. * Ambulatory partic…
Location
- St. Jude Children's Research HospitalMemphis, Tennessee