This infographic is intended for US healthcare professionals.
Neurol AMJ. 2026; https://doi.org/10.33590/neurolamj/LBKK2593
Spinal Muscular Atrophy:
A Disease of Both Muscles and Motor Neurons
This infographic was sponsored by Scholar Rock, Inc.
POLL QUESTION 1
Do you consider SMA to be a disease of:
A.
B.
C.
SMA IMPACTS THE ENTIRE MOTOR UNIT
Muscles
The motor neurons
Both
Healthy motor neuron
SMN protein
Healthy muscle
The SMN protein maintains motor neurons in a healthy motor unit, comprising both motor neurons and muscle.1
DESPITE ADVANCES WITH SMN-TARGETED TREATMENTS, MANY PEOPLE LIVING WITH SMA EXPERIENCE CONTINUED WEAKNESS AND PROGRESSIVE MUSCLE ATROPHY
The last 10 years have been transformative for SMA treatment, with the approval of three SMN-targeted therapies.6
Nusinersen
Onasemnogene abeparvovec
Risdiplam
However, significant disability persists among people living with SMA, including impacts on mobility, breathing, and eating.1
Mobility
Breathing
Eating
TREATING THE WHOLE MOTOR UNIT
Current FDA-approved SMA treatments increase the level of SMN protein to slow neuron degeneration.1
With SMN treatments targeting neuron stability, a dual-mechanism treatment approach that targets the muscles has the potential to improve motor function and overall quality of life.1
One potential target is myostatin.1
Current SMA therapy1
Muscle-targeted therapy1
MYOSTATIN AS A POTENTIAL THERAPEUTIC TARGET
Myostatin protein is a potential therapeutic target for SMN-independent SMA therapy.1
Bone
Tendon
Muscle bundle
Blood vessel
POLL QUESTION 2
How about now? Do you consider SMA to be a disease of:
KEY LEARNINGS
SMA is a disease that impacts both motor neurons (nerves) and muscles.2-5
So far, all approved therapies target the motor neuron.1
There is an opportunity to further increase motor function and muscle health by directly targeting the whole motor unit.1,7
Current SMA therapy1
Muscle-targeted therapy1
SMA is a neuromuscular disease caused by biallelic deletion or mutation of the SMN1 gene, leading to irreversible degeneration of lower motor neurons in the spinal cord.2,3
Motor neuron degeneration begins
Muscle fiber atrophy worsens
Once motor neurons begin to degenerate, the denervated muscle fibers atrophy while the innervated fibers remain intact.
Motor neuron degeneration begins
Muscle fiber atrophy begins
Motor neuron degeneration worsens
Muscle fiber atrophy worsens
Continued motor neuron loss leads to progressive skeletal muscle weakness and atrophy, and further motor function decline.2,3
Myostatin protein is a potential therapeutic target for SMN-independent SMA therapy.1
Bundle of muscle fibers (fascicle)
Myostatin protein is a potential therapeutic target for SMN-independent SMA therapy.1
Muscle fiber
Predominantly expressed in the skeletal muscle, myostatin inhibits muscle growth to maintain muscle homeostasis.7*
Myostatin
*Mechanism is based on preclinical data.
REFERENCES
Day J et al. BMC Pediatr. 2022;22(1):632.
Ruggiero M et al. J Neuromusc Dis. 2025;DOI:10.1177/22143602251397438.
Gnazzo M et al. Int J Mol Sci. 2025;26:5858.
Grandi FC et al. JCI Insight. 2024;9(20):e180992.
Lee JC et al. Human Mol Genet 2025;34(4)347-67.
Weng WC et al. J Formosan Med Assoc. 2025;DOI:10.1016/j.jfma.2025.10.018.
Abati E et al. Cell Mol Life Sci. 2022;79(7):374.
Pirruccello-Straub M et al. Sci Rep. 2018;8:2292.
ABBREVIATIONS
SMA: spinal muscular atrophy; SMN: survival motor neuron.
A.
Muscles
B.
The motor neurons
C.
Both
Inactivation of myostatin may help address muscle weakness in SMA directly.1,7,8
Inactivation of myostatin
SMN protein
SMN protein
SMN protein