Improving Health of Mitochondria May Be a Viable ALS Treatment Option

Improving Health of Mitochondria May Be a Viable ALS Treatment Option

The amyotrophic lateral sclerosis (ALS) drug Rilutek (riluzole) prevents neuronal cell death in part by acting on mitochondria, suggesting that treatment approaches that target the way mitochondria signal within cells may be a viable approach to treating ALS.

The study, “Riluzole But Not Melatonin Ameliorates Acute Motor Neuron Degeneration and Moderately Inhibits SOD1-Mediated Excitotoxicity Induced Disrupted Mitochondrial Ca2+ Signaling in Amyotrophic Lateral Sclerosis,” also looked at whether melatonin had similar beneficial effects, but it failed to show that the factor could provide neuroprotection. The study was published in the journal Frontiers in Cellular Neuroscience.

While Rilutek has been shown to impact calcium and excessive glutamate signaling to provide neuroprotection in ALS, studies in models of degeneration indicate that the drug also impacts mitochondrial actions.

But since no studies have examined the issue in models of ALS, a researcher from the University of Göttingen in Germany decided to further characterize the molecular effects of the drug.

In addition, the study examined claims that the antioxidant molecule melatonin has beneficial effects on its own.

To trigger cell death in lab-grown motor neurons, the cells were treated with a chemical that disrupted mitochondrial energy-making processes. The study showed that Riluzole prevented the death of motor neurons exposed to a chemical while melatonin failed to do so. The treatment also blocked toxic glutamate signaling to a certain extent.

The researcher then repeated the experiments in brain slices from adult mice with a mutation in the SOD1 gene. The brain tissue with SOD1 mutations are common in patients with familial ALS, and the mice capture many of the features of human ALS.

Treating the brain tissue with the mitochondrial-disrupting chemical disrupted calcium signaling in mitochondria. Experiments revealed that Rilutek improved the abnormal calcium signaling, and further analyses indicated that mitochondrial metabolism and health also improved with Rilutek. In contrast, no such effects were seen when the brain tissue was treated with melatonin.

The idea that ALS can be treated by targeting mitochondria is also pursued by other researchers. Mitochondrial abnormalities in ALS may not necessarily be related to SOD1 (a protein linked to ALS), as a research team recently showed that the protein TDP-43 also disrupts mitochondrial processes in ALS.

3 comments

    • Magdalena Kegel says:

      Dear Nancy,
      I am not aware of any studies in which Rilutek (riluzole) has been studied in the context of mitochondrial disease. That said, it is currently not possible to exclude the possibility that it would be beneficial.

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