DALLAS — Leukocyte telomere length was associated with disability progression in multiple sclerosis (MS) patients independent of age, researchers reported here.
Shorter telomere length was tied to increased disability in both cross-sectional and longitudinal analyses after adjusting for chronological age, suggesting aging-related processes may contribute to neurological injury in MS, said Kristen Krysko, MD, of the University of California, San Francisco (UCSF), and colleagues, in an “Emerging Concepts in MS” session at the Americas Committee for Treatment and Research in Multiple Sclerosis forum.
“This is the first study to demonstrate that the ultimate marker of the biological clock — telomere length — is associated with measures of MS progression,” Krysko told MedPage Today.
While factors leading to disability in MS are complex, one variable consistently associated with faster time to disability milestones is older chronological age, Krysko noted.
Biological aging, including declining remyelination capacity and changes in immune responses, also may contribute to neurodegeneration, she added. Biological aging can vary widely, even among people with the same birthdate. Telomeres — proteins and nucleotide repeats at ends of chromosomes that shorten with each cell division — are well recognized as markers and drivers of downstream effects of biological aging.
To evaluate links between telomere length and disability progression, Krysko and colleagues looked at 516 patients with MS or clinically isolated syndrome (CIS) from the MS EPIC cohort at UCSF. The group was largely female (69%) with an average age of 43 at baseline and a median disease duration of 6 years.
In the sample, 367 patients had relapsing-remitting MS; 80 had CIS, 47 had secondary progressive MS, 17 had primary progressive MS, and 4 had progressive relapsing MS. The group had a median Expanded Disability Status Scale (EDSS) score of 1.5 at baseline (EDSS scores range from 0-10, with higher scores indicating worse disability).
Higher age (P<0.001) and longer disease duration (P<0.001) were associated with shorter leukocyte telomere length at baseline. For each standard deviation unit lower of telomere length, EDSS was 0.27 units higher (95% CI 0.13-0.42, P<0.001) and total brain volume was 7.4 mm3 lower (95% CI 0.1-14.7, P=0.047), after adjusting for age, disease duration, and sex.
In longitudinal analyses, patients with lower baseline telomere length consistently had higher EDSS and lower brain volumes over 10 years.
As part of their study, the researchers matched a subset of 23 patients who developed secondary progressive MS during follow-up with 23 patients who remained with relapsing MS. Among the 23 matched pairs, change in telomere length over 10 years predicted change in EDSS: for each standard deviation unit decrease in leukocyte telomere length, EDSS was 0.34 units higher (95% CI, 0.08-0.61, P=0.012).
“These results imply that biological aging pathways may directly contribute to MS progression,” said co-author Jennifer Graves, MD, PhD, of the University of California, San Diego.
Oxidative stress, decline in remyelination and resilience to injury, changes in immune function, and comorbidities and lifestyle all may be factors, the researchers noted. “This work suggests that targeting aging-related pathways may be a strategy for treating progressive MS,” Graves told MedPage Today.
DNA availability in this study limited the ability to measure leukocyte telomere length in all patients over time, the researchers noted. The study also had low power to detect associations in the subset of 23 matched pairs.
The study was funded by the National Multiple Sclerosis Society. Krysko disclosed support from a Sylvia Lawry award from the National MS Society and Biogen MS.
Graves disclosed relevant relationships with the National MS Society, Race to Erase MS, Biogen, Genentech, Novartis, and Genzyme.