Metabolic analysis of platelets from patients with Friedreich’s ataxia (FA), using liquid chromatography–mass spectrometry (LC-MS), revealed metabolic alterations that may be the focus of future therapeutics, according to a study, “Stable isotopes and LC–MS for monitoring metabolic disturbances in Friedreich’s ataxia platelets,” published in the Bioanalysis journal.
FA is a genetic disease caused by a defect, a trinucleotide GAA expansion, in the Fxn gene leading to the production of a defective mitochondria protein called frataxin. Currently, no therapy is available for Friedreich ataxia’s patients either to delay disease progression or ameliorate patients’ symptoms, although accompanying complications can be treated.
Since a series of processes depend on healthy mitochondria, such as metabolic reactions, lack of frataxin protein associates with metabolic abnormalities, which ultimately lead to neurodegeneration and cardiomyopathy. However, the difficulty in accessing both neuronal and cardiac tissues has delayed metabolic comprehensive analyses of these tissues in FA patients.
Following a previous finding that isolated human platelets (also known as thrombocytes, a crucial component of blood) can serve as a platform for metabolic profiling, researchers hypothesized that platelets could be used as surrogate diagnostic tissue for diseases that lead to global metabolic changes, such as FA.
The research team used LC-MS to determine if platelets isolated from FA patients exhibited differences in metabolism when compared to platelets extracted from healthy controls. They enrolled a total of 10 patients and 10 healthy controls, and used marked isotopes for glucose and palmitate, two crucial players in key metabolic reactions.
Researchers found that platelets from FA patients showed a marked decrease in glucose incorporation, while the levels of palmitate-derived acyl-CoA thioesters were increased when compared to healthy controls. These results showed that platelets from FA patients have a differential mitochondrial metabolism. Moreover, using isotopic tracers coupled with analysis by LC–MS is an efficient technique identifying these changes.
These data suggest that using isotope labeling coupled with LC-MS could be a possible biomarker methodology that may be used in future studies to investigate and monitor therapeutic approaches to treat Friedreich’s ataxia.