Understanding metabolic flexibility: a potential key to unlocking metabolic therapies in amyotrophic lateral sclerosis?

If metabolic dysfunction is not the cause of ALS then it certainly is an early, important cause of the disease because it can affect disease progression rates (Steyn et al., 2018). [...]in depth understanding of the metabolic pathways and how they are affected in ALS could lead to therapies that slow down the disease progression and increase the quality of life of people with the disease. [...]it could be argued that patient heterogeneity is not recapitulated to the same extent, which contributes to the lack of therapeutic translation observed in the ALS field between animal models and patients. [...]a lack of a successful translatable animal model makes the use of human models of disease such as fibroblasts all the more relevant, especially as they can be readily reprogrammed into inducible neuronal progenitor cells (Meyer et al., 2014). [...]using fibroblast-derived induced neuronal progenitor cells differentiated into iAstrocytes we were able to assess how the metabolic profile and metabolic flexibility was altered by the reprogramming process. [...]disruption to these processes leads to toxicity in the event of disrupted metabolic fuel supplies to the glycolytic and mitochondrial energy generation pathways.