Heart problems can be a symptom of Friedreich’s ataxia (FA). In 2022, Prof Richard Festenstein of Imperial College London received a grant from Ataxia UK to generate a heart cell model in FA in order to understand why FA affects the heart.
To do this, Prof Festenstein and his team used blood stem cells taken from people with and without FA, to make heart cells in their lab. Stem cells are cells which, under certain conditions in the laboratory, can become other types of cells. It is important to develop good models of FA so that we can understand the condition and test potential treatments. Festenstein and his team found that part of the mitochondria, the energy centres of cells, known as mitochondrial complex 1 (MC1) was reduced in density in this cell model.
Since then, Prof Festenstein has gone on to receive further funding to continue his ataxia research and has recently published a paper looking at MC1 as a potential new biomarker of FA disease progression in humans and mice. FA is caused by mutations in the frataxin gene, leading to reduced levels of the frataxin protein and neurodegeneration. Loss of frataxin impacts activity in part of the mitochondria known as mitochondrial complex 1 (MC1), suggesting that MC1 may be a potential biomarker of frataxin levels and function in FA.
In this study, a type of non-invasive brain scan called PET imaging was used to look at mitochondria from brain and heart cells of mice with FA (12) and adults with FA (12) compared with mice without FA (12) and adults without FA (15). Both brain scans and scans of the heart muscle in mice and people with FA showed that the MC1 region of mitochondria was less dense than in mice and people without FA, consistent with the findings from Festenstein’s Ataxia UK-funded study.
He and his team hope that this non-invasive imaging method can be used to monitor FA disease progression in people with FA, which may be a useful tool in clinical trials. Further research in higher numbers of mice and people with FA is needed to understand whether mitochondrial MC1 density may be a valid biomarker for clinical trials in FA. Read the paper here.
