Telomere Length May Be a Helpful Biomarker in Friedreich's Ataxia Patients

Telomeres are short nucleotide sequences at the end of chromosomes that protect genetic information. They have been analogized to the tips of shoelaces, called aglets, that keep the laces from fraying. Inflammation and increased levels of oxidative stress can affect telomere length, and several neurodegenerative disorders, such as Alzheimer’s disease, Huntington’s disease and spinocerebellar ataxias have characteristic telomere shortening, often resulting from immune system insult and oxidative stress that follows. Shortened telomeres have been associated with age-related diseases such as cardiovascular diseases, neurodegenerative disorders and certain types of cancer

Leukocyte telomere length (LTL), specifically, might hold some answers to Friedreich's ataxia (FA) progression, according to Daniela Scarabino, Ph.D., from the Institute of Molecular Biology and Pathology at the National Research Council in Rome, Italy, and colleagues in a study published in Movement Disorders this month.

Seeking to establish LTL as a potential biomarker for monitoring disease progression, the study explored the relationship between LTL and various clinical and genetic factors in a cohort of FA patients, including biallelic patients, heterozygous carriers, and healthy controls. The hallmark feature of FA, frataxin protein deficiency, leads to oxidative stress, mitochondrial dysfunction and inflammation, which affecttelomere length.

Telomere shortening is linked to cell division limits, aging, disease risk, cellular senescence and is a biomarker for health and disease progression. Monitoring telomere length can provide insights into disease susceptibility, severity, and progression.

LTL was quantified using real-time polymerase chain reaction in a cohort comprised of 61 biallelic FA patients, 29 heterozygous carriers, and 87 age-matched healthy controls. The researchers assessed the relationship between LTL, age at blood sampling, repeating frataxin gene sequences, disease duration and various clinical parameters, including the presence of cardiomyopathy and diabetes.

The findings revealed a notable age-dependent behavior in LTL among the studied groups. For individuals 35 and younger, FA patients exhibited longer LTL than controls, while the opposite was true for those over 36 and older. Additionally, heterozygous carriers maintained longer LTL across all ages.

The study found a positive correlation between specific repeating DNA sequences encoding frataxin and LTL and an inverse relationship with age at blood sampling. Importantly, shorter LTL was significantly associated with the presence of cardiomyopathy, providing a potential link between telomere shortening and certain clinical manifestations of FA.

The analysis suggested that LTL was not only altered in FA but may serve as a valuable biomarker for tracking disease progression. The relationship between telomere dynamics and FA is, however, complex. According to Scarabino, how an initial increase in LTL during early cellular replication can be followed by accelerated shortening due to oxidative stress and inflammation requires further investigation.