Researchers are developing a new analytical method, using patients’ platelets, that enables rigorous quantification of frataxin, the protein lacking in patients with Friedreich’s ataxia (FA).
Findings of the study ”Liquid Chromatography-High Resolution Mass Spectrometry Analysis of Platelet Frataxin as a Protein Biomarker for the Rare Disease Friedreich’s Ataxia,” were published in the journal Analytical Chemistry.
FA is a rare genetic disease that usually begins in childhood and causes gradual impairment of motor coordination due to degeneration in the spinal cord and the cerebellum, the brain area that controls balance and movement. About one in 50,000 people in the U.S. have FA.
The disease is caused by a mutation in the FXN gene, which involves repeats of the GAA sequence of nucleotides (the building blocks of DNA). The number of GAA repeats correlates with disease severity. Mutations in FXN lead to reduced production of frataxin, which is present in mitochondria (the body’s power plants). In turn, this results in impairment of energy metabolism in the cells.
Although new therapies are being tested, no treatments are approved yet for FA. Increasing frataxin levels is the primary goal of current therapy strategies. However, frataxin cannot be detected in the blood.
So, after using platelets (the cells involved coagulating blood) to develop a strategy to monitor changes in mitochondrial metabolism, researchers at the University of Pennsyslvania developed a method that enables more direct and sensitive quantification of mature frataxin in platelets from patients with FA. “… platelets have 86% of the mitochondria present in whole blood and a half-life of only 10 days making them an attractive alternative [to red blood cells],” the researchers wrote.
The method was able to detect very low levels of frataxin. In addition, it showed 100 percent sensitivity and specificity to differentiate controls from FA patients. As expected, FA patients showed significantly less platelet frataxin than controls.
Of note, the correlation between frataxin levels and GAA repeats did not reach statistical significance. This may have been due to the low number of participants (14, seven in each group), the investigators observed.
“The assay should make it possible to rigorously monitor the effects of therapeutic interventions on frataxin expression in this devastating disease,” the researchers wrote.
In addition, “this method also provides an approach to monitor new therapies that are being developed for rare genetic diseases of aberrant protein expression such as [Duchenne muscular dystrophy] and [spinocerebellar ataxia 1],” they added.