Key result
Rapamycin and resveratrol improve neuromuscular function and extend lifespan in a C. elegans SMA model.
Why the study?
Although autophagy dysregulation has been implicated in spinal muscular atrophy pathology, the therapeutic benefit of modulating this pathway remained controversial.
Does pharmacological activation of autophagy improve neuromuscular function and extend lifespan in a C. elegans model of SMA?
Does pharmacological activation of autophagy improve neuromuscular function and extend lifespan in a C. elegans model of SMA?
Pharmacological activation of autophagy improves neuromuscular function and extends lifespan in a C. elegans model of SMA, suggesting a potential combinatorial treatment strategy.
Autophagy activation is hypothesis-generating in SMA models; leaves open translation to mammalian systems and clinical testing.
Spinal muscular atrophy (SMA) is a severe neuromuscular disorder caused by homozygous deletions or mutations in the SMN1 gene, resulting in reduced levels of the ubiquitously expressed survival motor neuron protein and progressive degeneration of lower motor neurons. Although autophagy dysregulation has been implicated in SMA pathology, the therapeutic benefit of modulating this pathway remains controversial. Here, we screened autophagy modulators in a previously characterized Caenorhabditis elegans SMA model. We identified that pharmacological activation of autophagy, but not inhibition, significantly improved neuromuscular function, as indicated by two independent functional readouts: pharyngeal pumping and locomotor activity assays. These beneficial effects were validated in an independent severe C. elegans SMA mutant allele and were observed in metabolically active and inactive food conditions. Furthermore, autophagy activators significantly extended lifespan of SMA nematodes without affecting controls. Notably, rapamycin and resveratrol increased endogenous SMN-1 protein levels, and improved neuromuscular function was dependent on an intact autophagy pathway. Collectively, our findings support enhancing autophagic activity as a combinatorial treatment strategy for SMA patients.
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Rashid et al. (2026) studied Spinal muscular atrophy (SMA). Pharmacological activation of autophagy (rapamycin and resveratrol) vs. Controls was evaluated on Neuromuscular function (pharyngeal pumping and locomotor activity) and lifespan. Pharmacological activation of autophagy using rapamycin and resveratrol significantly improved neuromuscular function and extended lifespan in a C. elegans model of spinal muscular atrophy.
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