SMA impacts all aspects of the motor unit
SMA impacts all aspects of the motor unit1,2
The result is an irreversible loss of motor neurons and progressive muscle loss2,3
Muscle atrophy in SMA can cause continuous motor function decline and can diminish activities of daily living that impact independence4:
Eating2
Holding head upright2
Walking2
Breathing2
Every sweep of your arm, every lift of a cup to your mouth to take a sip of water, you feel [SMA] all the time.
Mindy
Treated with ISEMBYLD
Paid spokesperson
Muscle loss is a defining characteristic of SMA2
It is important to directly target both key parts of the motor unit: the motor neuron and the muscle2
IT’S URGENT TO ACT NOW5
Although motor neurons can deteriorate and die over time, the muscle can still gain function5
TARGET TWO KEY PARTS OF THE MOTOR UNIT2
Due to the progressive nature of SMA, motor function can decline over time, despite ongoing SMN2-targeted treatment2,8,9
These graphs include open-label extension trial data without an untreated control group. These findings are not as definitive as those from a randomized, controlled study.
CHERISH was a phase 3, randomized, double-blind, sham-controlled study to evaluate the efficacy and safety of nusinersen in children with later-onset SMA. SHINE was an open-label extension study for patients with SMA who previously participated in investigational studies of nusinersen, such as CHERISH.
HFMSE=Hammersmith Functional Motor Scale–Expanded; SE=standard error; SMN=survival motor neuron.
These graphs include open-label extension trial data without an untreated control group. These findings are not as definitive as those from a randomized, controlled study.
SUNFISH was a 2-part clinical trial of risdiplam in a broad and heterogeneous patient population with types 2 and 3 SMA (aged 2-25 years).9
aClinical cutoff date: October 2, 2023. bClinical cutoff date: September 6, 2019. Patients in the placebo group received placebo for 12 months followed by risdiplam treatment for 48 months.9 cNumber of patients with valid results = number of patients with an available total score (result) at respective time points. Intent-to-treat patients.9 *±95% CI. Baseline is the last measurement prior to the first dose of risdiplam or placebo.9
HFMSE=Hammersmith Functional Motor Scale–Expanded.
When it comes to motor function, what really affected Lily was keeping up with her peers and living life.
Tracy
Daughter, Lily, is treated with ISEMBYLD
Paid spokesperson
Muscle atrophy affects multiple parts of the body, negatively impacting the motor function of children and adults living with SMA10
% of patients who agree SMA-induced muscle weakness has impacted their ability to do certain activities10,*
*Two complementary, web-based surveys were distributed by researchers in August 2024 among 40 children (aged <1-17, mean age 8.3 years; represented by caregiver proxies) and 68 adults (mean age 37.5 years) living with SMA who were nonambulant and currently receiving risdiplam or nusinersen. Recruitment was facilitated by a patient advocacy organization (Cure SMA). Results were published in the Annals of Clinical and Translational Neurology.10
SMA=spinal muscular atrophy; SMN=survival motor neuron.
MUSCLE WEAKNESS PERSISTS9,*
95%
of children and adults who were currently receiving an SMN2-targeted treatment reported persistent muscle weakness. An overwhelming majority report weakness that impacts their motor function and daily activities (n=108).
*Two complementary, web-based surveys were distributed by researchers in August 2024 among 40 children (aged <1-17, mean age 8.3 years; represented by caregiver proxies) and 68 adults (mean age 37.5 years) living with SMA who were nonambulant and currently receiving risdiplam or nusinersen. Recruitment was facilitated by a patient advocacy organization (Cure SMA). Results were published in the Annals of Clinical and Translational Neurology.10
SMA=spinal muscular atrophy; SMN=survival motor neuron.
Over time, SMA can devastate the motor unit, which includes the motor neuron and the muscle1,2
MOA
ISEMBYLD directly targets the muscle to treat SMA.11 See the mechanism of action.
RELATED FAQs
How do the motor neuron and muscle each contribute to motor function?
Motor function depends on motor neuron and muscle, both distinct elements of the motor unit. Motor neurons transmit nerve impulses, which travel down the axon to the muscle. Muscle is innervated by motor neurons, and receives signals that prompt muscle fiber contraction.1
What is the impact of SMA on muscle?
The deterioration of motor neurons caused by a mutation of the SMN1 gene directly leads to the muscle atrophy that is a characteristic of SMA. As a result of muscle atrophy, people with SMA can experience motor function loss and associated complications.2
References:
1. Le Verche V, et al. In: Sumner CJ, Paushkin S, Ko CP, eds. Spinal Muscular Atrophy: Disease Mechanisms and Therapy. Elsevier; 2017:341-356. 2. Day JW, Howell K, Place A, et al. Advances and limitations for the treatment of spinal muscular atrophy. BMC Pediatr. 2022;22(1):632. 3. Mercuri E, Finkel RS, Muntoni F, et al. Diagnosis and management of spinal muscular atrophy: part 1: recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscul Disord. 2018;28(2):103-115. 4. Song W, Ke X. Rehabilitation management for patients with spinal muscular atrophy: a review. Orphanet J Rare Dis. 2025 Jul 10;20(1):352. doi: 10.1186/s13023-025-03888-w. PMID: 40640932; PMCID: PMC12243183. 5. Finkel RS, Crawford TO, Darras BT, et al. Advancing treatment of spinal muscular atrophy through inhibition of the myostatin signaling pathway. Expert Rev Neurother. 2026;26(3):211-225. 6. Antonaci L, Pera MC, Mercuri E. New therapies for spinal muscular atrophy: where we stand and what is next. Euro J Pediatr. 2023;182:2935-2942. 7. Ting LH, Chiel HJ. Muscle, biomechanics, and implications for neural control. In: Hooper SL, Büschges A, eds. Neurobiology of Motor Control: Fundamental Concepts and New Directions. John Wiley & Sons; 2017:365-416. 8. Finkel RS, Farrar MA, Krosschell KJ, et al. Final safety and efficacy data from the SHINE study in participants with infantile-onset and later-onset SMA. Poster presented at: Cure SMA Research and Clinical Care Meeting; June 5-7, 2024; Austin, TX. Poster 95. 9. Servais L, Day JW, Deconinck N, et al. SUNFISH Parts 1 and 2: 5-year efficacy and safety data of risdiplam in Types 2 and 3 spinal muscular atrophy (SMA). Presented at: MDA Clinical & Scientific Conference; Mar 16-19, 2025; Dallas, Texas. Poster 94. 10. Parsons JA, Land N, Maravic MC, et al. Remaining burden of spinal muscular atrophy among treated patients: a survey of patients and caregivers. Ann Clin Transl Neurol. 2025;12(10):2020-2035. 11. ISEMBYLD. Prescribing information. Scholar Rock, Inc; 2026.