Characterizing Perceived Physical Fatigability in Nusinersen-treated SMA

Characterizing Perceived Physical Fatigability in Nusinersen-treated Adolescents and Adults: The SMA EFFORT

The purpose of this project is to investigate the utility of the SMA EFFORT, an SMA-specific patient-reported outcome measure, to assess perceived physical fatigability that is anchored to intensity and duration of activities. We aim to characterize perceived physical fatigability (PPF) in a diverse cohort of people with SMA (pwSMA) and evaluate the change of PPF before and after nusinersen dosing.

Fatigue and fatigability are symptoms often experienced by people living with spinal muscular atrophy (pwSMA). Nusinersen is shown to extend survival and improve motor function, but fatigue and fatigability persist. Treated patients report changes in their ability to complete repetitive physical activities but a way for measuring this has not been created. While tests completed in the clinic by individuals with SMA highlight that fatigability is an important part of the SMA experience,we do not fully understand how pwSMA experience fatigability with everyday tasks. Anecdotal reports of pwSMA suggest a waning effect in endurance toward the end of their treatment window, however this change has not been measured.The SMA EFFORT is specifically designed for pwSMA and aims to better understand how they feel when completing daily physical activities.

Inclusion Criteria:

1. All types of 5qSMA (homozygous deletion or point mutation of the SMN1 gene and any number of SMN2 copies)
2. Receiving a stable dosing regimen of 12 or 28 mg nusinersen for at least 6 months

Exclusion Criteria:

1. An injury or surgery within the previous 3 months that would impact their ability to perform in-clinic function and/or fatigability assessments
2. Enrolled in an ongoing clinical trial, or extension study, expanded access program, or long-term registry of an investigational or recently approved medication
3. Receiving adjuvant and/or dual therapy (e.g., muscle-targeted, NMJ, or symptomatic treatments)