Promising New Treatment Emerges for Spinal Muscular Atrophy

Restoring defected mitochondrial function may be a new target for rare genetic disorder.

Researchers have found a potential new target for treating spinal muscular atrophy (SMA), which involves restoring impaired mitochondrial function.

Mitochondria’s involvement in SMA was first discovered when researchers analyzed the gene expression profiles of motor neurons from SMA and control mice. The findings were published in Human Molecular Genetics.

“Restoring mitochondrial function might be a new treatment strategy for SMA,” said senior study author Yongchao Ma. “While the genetic cause of this devastating disease has been identified, out study describes how mitochondrial dysfunction might contribute to motor neuron destruction even before the onset of symptoms. Our findings provide new insights into SMA pathogenesis, which is crucial to developing new therapies.”

While researchers analyzed the gene expression profiles, to their surprise, they found that the genes related to many mitochondrial functions were significantly dysregulated in SMA motor neurons.

“This discovery was unexpected and led us to test whether mitochondrial functions were changed in motor neurons from SMA mouse models,” Ma said.

During the study, researchers used sophisticated technology to show that mitochondria in SMA motor neurons produce energy at a slower rate, resulting in the depletion of the nerve. SMA mitochondria were less healthy, as made evident by its decreased membrane potential.

Furthermore, there was an increase in oxidative stress levels, which is toxic to the neuron. Additional impairment was seen as well, in the movement of the mitochondria, which would cause it to get stuck at the junction between nerve and muscle, leaking toxins, and eventually destroying the connection.

The mitochondria in SMA motor neurons was also fragmented and swollen, which authors noted is consistent with the functional defects that were measured by the study.

“Motor neurons have high energy demands, which would make them highly sensitive to defects in their mitochondria,” Ma said. “These defects might lead to the symptom of motor neuron degeneration in SMA.”