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Biologic aging as measured by leukocyte telomere length (LTL) is associated with multiple sclerosis (MS) disability progression independent of chronological age, according to a study presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Kristen M. Krysko, MD, clinical fellow in neurology at University of California, San Francisco (UCSF).
Dr. Kristen M. Krysko

Shorter telomere length is associated with increased MS disability in cross-sectional and longitudinal analyses, said Kristen M. Krysko, MD, clinical fellow in neurology at University of California, San Francisco. The results suggest that biologic aging may contribute to neurologic injury in MS and that “targeting aging-related mechanisms may be a potential therapeutic strategy,” said Dr. Krysko.

If validated, telomere length may be a biomarker that neurologists could use to guide decisions about MS treatment, said principal investigator Jennifer Graves, MD, PhD, also of UCSF.

“Factors leading to MS progression are not fully understood,” Dr. Krysko said. “But consistently, older chronological age has been associated with a faster time to disability milestones.” Aging may reduce remyelination capacity and alter immunologic responses. Telomere shortening, a marker of cellular aging, is “the ultimate biological clock.” It has been associated with cardiovascular disease, dementia, and autoimmune diseases, and one study found that patients with primary progressive MS have shorter telomere length, compared with controls.

To assess whether LTL is associated with clinical disability and brain volume in patients with MS, the researchers analyzed data from 516 adults with MS or clinically isolated syndrome in the EPIC cohort study at UCSF. Telomere length was measured on stored baseline DNA samples and expressed as the ratio of telomere to a single-copy gene.

The patients had an average age of 43 years, median disease duration of 6 years, and median Expanded Disability Status Scale (EDSS) score of 1.5; about 70% were women. The average telomere length was 0.97.

 

 


Older age and longer disease duration were associated with shorter LTL. For every 0.2-unit decrease in telomere length, EDSS score increased by 0.41. After adjusting for age, disease duration, and sex, every 0.2-unit decrease in telomere length was associated with a score increase of 0.27 on the EDSS. LTL also was associated with total brain volume and total white matter volume.

In addition, the investigators conducted a case control study that included a subset of 23 patients who developed secondary progressive MS during follow-up and had DNA available at multiple time points. The researchers matched these patients with 23 patients who continued to have relapsing MS. Patients were matched by age, sex, and disease duration. An adjusted analysis found that change in LTL was predictive of change in EDSS over 10 years such that every 0.2-unit decrease in LTL was associated with a 0.34-unit increase in EDSS.

Longitudinal analyses found that baseline LTL predicted higher levels of disability over time.

The study was funded by the National Multiple Sclerosis Society.

SOURCE: Krysko KM et al. ACTRIMS Forum 2019, Abstract 289.

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Biologic aging as measured by leukocyte telomere length (LTL) is associated with multiple sclerosis (MS) disability progression independent of chronological age, according to a study presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Kristen M. Krysko, MD, clinical fellow in neurology at University of California, San Francisco (UCSF).
Dr. Kristen M. Krysko

Shorter telomere length is associated with increased MS disability in cross-sectional and longitudinal analyses, said Kristen M. Krysko, MD, clinical fellow in neurology at University of California, San Francisco. The results suggest that biologic aging may contribute to neurologic injury in MS and that “targeting aging-related mechanisms may be a potential therapeutic strategy,” said Dr. Krysko.

If validated, telomere length may be a biomarker that neurologists could use to guide decisions about MS treatment, said principal investigator Jennifer Graves, MD, PhD, also of UCSF.

“Factors leading to MS progression are not fully understood,” Dr. Krysko said. “But consistently, older chronological age has been associated with a faster time to disability milestones.” Aging may reduce remyelination capacity and alter immunologic responses. Telomere shortening, a marker of cellular aging, is “the ultimate biological clock.” It has been associated with cardiovascular disease, dementia, and autoimmune diseases, and one study found that patients with primary progressive MS have shorter telomere length, compared with controls.

To assess whether LTL is associated with clinical disability and brain volume in patients with MS, the researchers analyzed data from 516 adults with MS or clinically isolated syndrome in the EPIC cohort study at UCSF. Telomere length was measured on stored baseline DNA samples and expressed as the ratio of telomere to a single-copy gene.

The patients had an average age of 43 years, median disease duration of 6 years, and median Expanded Disability Status Scale (EDSS) score of 1.5; about 70% were women. The average telomere length was 0.97.

 

 


Older age and longer disease duration were associated with shorter LTL. For every 0.2-unit decrease in telomere length, EDSS score increased by 0.41. After adjusting for age, disease duration, and sex, every 0.2-unit decrease in telomere length was associated with a score increase of 0.27 on the EDSS. LTL also was associated with total brain volume and total white matter volume.

In addition, the investigators conducted a case control study that included a subset of 23 patients who developed secondary progressive MS during follow-up and had DNA available at multiple time points. The researchers matched these patients with 23 patients who continued to have relapsing MS. Patients were matched by age, sex, and disease duration. An adjusted analysis found that change in LTL was predictive of change in EDSS over 10 years such that every 0.2-unit decrease in LTL was associated with a 0.34-unit increase in EDSS.

Longitudinal analyses found that baseline LTL predicted higher levels of disability over time.

The study was funded by the National Multiple Sclerosis Society.

SOURCE: Krysko KM et al. ACTRIMS Forum 2019, Abstract 289.

 

Biologic aging as measured by leukocyte telomere length (LTL) is associated with multiple sclerosis (MS) disability progression independent of chronological age, according to a study presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Kristen M. Krysko, MD, clinical fellow in neurology at University of California, San Francisco (UCSF).
Dr. Kristen M. Krysko

Shorter telomere length is associated with increased MS disability in cross-sectional and longitudinal analyses, said Kristen M. Krysko, MD, clinical fellow in neurology at University of California, San Francisco. The results suggest that biologic aging may contribute to neurologic injury in MS and that “targeting aging-related mechanisms may be a potential therapeutic strategy,” said Dr. Krysko.

If validated, telomere length may be a biomarker that neurologists could use to guide decisions about MS treatment, said principal investigator Jennifer Graves, MD, PhD, also of UCSF.

“Factors leading to MS progression are not fully understood,” Dr. Krysko said. “But consistently, older chronological age has been associated with a faster time to disability milestones.” Aging may reduce remyelination capacity and alter immunologic responses. Telomere shortening, a marker of cellular aging, is “the ultimate biological clock.” It has been associated with cardiovascular disease, dementia, and autoimmune diseases, and one study found that patients with primary progressive MS have shorter telomere length, compared with controls.

To assess whether LTL is associated with clinical disability and brain volume in patients with MS, the researchers analyzed data from 516 adults with MS or clinically isolated syndrome in the EPIC cohort study at UCSF. Telomere length was measured on stored baseline DNA samples and expressed as the ratio of telomere to a single-copy gene.

The patients had an average age of 43 years, median disease duration of 6 years, and median Expanded Disability Status Scale (EDSS) score of 1.5; about 70% were women. The average telomere length was 0.97.

 

 


Older age and longer disease duration were associated with shorter LTL. For every 0.2-unit decrease in telomere length, EDSS score increased by 0.41. After adjusting for age, disease duration, and sex, every 0.2-unit decrease in telomere length was associated with a score increase of 0.27 on the EDSS. LTL also was associated with total brain volume and total white matter volume.

In addition, the investigators conducted a case control study that included a subset of 23 patients who developed secondary progressive MS during follow-up and had DNA available at multiple time points. The researchers matched these patients with 23 patients who continued to have relapsing MS. Patients were matched by age, sex, and disease duration. An adjusted analysis found that change in LTL was predictive of change in EDSS over 10 years such that every 0.2-unit decrease in LTL was associated with a 0.34-unit increase in EDSS.

Longitudinal analyses found that baseline LTL predicted higher levels of disability over time.

The study was funded by the National Multiple Sclerosis Society.

SOURCE: Krysko KM et al. ACTRIMS Forum 2019, Abstract 289.

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