PTEN Depletion Found To Decrease Spinal Muscular Atrophy Disease Severity, Prolongs Survival Modestly in Animal Studies

Findings from a new study published in the journal Molecular Therapy offer a promising therapeutic strategy for patients with Spinal Muscular Atrophy (SMA).

Spinal muscular atrophy (SMA) is an autosomal recessive disorder that causes loss of motor neurons and atrophy of the muscle, with patients presenting loss of strength in proximal muscles. SMA is caused by mutations or deletion of the telomeric copy of the survival motor neuron 1 gene (SMN1) that results in reduced SMN protein levels. However, it remains unclear why SMN deficiency affects motor neurons.

SMN is expressed and involved in the RNA metabolism. Evidence has shown that one of the features of SMN defective motor neurons is an axon elongation defect. Furthermore, studies have found that in SMA there is a decrease in mRNA levels, suggesting that SMN may be necessary for mRNA transport along axons. At the moment restoring the SMN expression is being investigated as a potential strategy in SMA mouse models, however, modulating the expression of other genes may offer extra motor neuron protection through alternative mechanisms and molecular pathways.

In their research entitled “PTEN Depletion Decreases Disease Severity and Modestly Prolongs Survival in a Mouse Model of Spinal Muscular Atrophy,” Daniel Little and colleagues based on previous findings that indicated that PTEN depletion increases survival of SMN-deficient motor neurons, aimed that examining the impact of the PTEN modulation in a in vitro SMA mice model.

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The analysis revealed that PTEN modulation ameliorated the severity of neuromuscular junction pathology, after mice received an injection that silenced the PTEN gene expression via RNA. Then the researchers compared the results of a treatment injection aimed at suppressing the PTEN and observed an increase the life-span of SMA mice in a mean survival of 30 days, compared to mice without treatment (mean survival of 10 days).

Results from this study revealed that PTEN depletion modifies SMA expression in mice models with SMA. The team of researchers strongly suggest that therapies that target lowering PTEN expression can work as a potential treatment strategy for SMA. However, further studies are necessary.