Through magnetic resonance technology (MRI), Habets and colleagues have discovered that mitochondrial dysfunction and muscle remodeling occur in spinal muscular atrophy (SMA), according to a study published in Brain. 

“There is a clear need for deeper understanding of underlying causes of muscle weakness and exercise intolerance in patients with this disease to further optimize treatment strategies,” the research team wrote. Animal studies have suggested that intrinsic abnormalities of the muscle, including mitochondrial dysfunction, feature significantly in SMA etiology. 

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Habets et al decided to use MRI to conduct in-depth research into muscle behavior and function in patients with SMA. The researchers designed their study to include in vivo clinical investigation of muscle bioenergetics. They recruited patients with SMA (n=15) and healthy age- and sex-matched control participants (n=15).

The imaging modality judged to be most suitable for this study was MRI and 31phosphorus magnetic resonance spectroscopy. Bioenergetic parameters, such as blood lactate and muscle dynamic recovery constants, were measured.

The results demonstrated significant atrophy of the triceps (but not the biceps) in patients with SMA. Maximum voluntary contraction force was 1.4-fold lower for both arm muscles in SMA patients than in control subjects.

In addition, the researchers observed altered intramuscular inorganic phosphate accumulation and a rise in blood lactate levels during arm-cycling in patients with SMA, which correlates with muscle weakness. Mitochondrial adenosine triphosphate (ATP) synthetic dysfunction was demonstrated in SMA patients by slower postexercise metabolic recovery in residual intramuscular white myofibers.

This study is significant because it “provides first in vivo evidence in patients that degeneration of motor neurons and associated musculature causing atrophy and muscle weakness in 5q [SMA] type 3 and 4 is aggravated by disproportionate depletion of myofibers that contract fastest and strongest,” according to Habets et al. The findings of this study could have an impact on the design of future studies on SMA muscle weakness.


Habets LE, Bartels B, Asselman FL, et al. Magnetic resonance reveals mitochondrial dysfunction and muscle remodelling in spinal muscular atrophy. Brain. Published November 11, 2021. doi:10.1093/brain/awab411