Abstract Details

Title Leukocyte telomere length is associated with disability progression in multiple sclerosis independent of chronological age

Topic Multiple Sclerosis

Presentation(s) S37 - MS Biomarkers (2:28 PM-2:39 PM)

Poster/Presentation
Number 009

Background Older chronological age is associated with faster time to disability milestones in MS. Aging-related processes may contribute to neurodegeneration underlying MS progression.

Objective To assess whether biological aging as measured by leukocyte telomere length (LTL) is associated with clinical disability and brain volume in MS.

Design/Methods Adults with MS/CIS in the EPIC cohort study at UCSF were included. LTL was measured on stored baseline DNA samples by quantitative PCR and expressed as the ratio of abundance of telomere vs. a single copy gene (T/S). Expanded Disability Status Scale (EDSS) and high-resolution 3D T1-weighted brain MRI were performed at baseline and follow-up. Associations of baseline LTL with cross-sectional and longitudinal clinical outcomes were assessed using simple and mixed effects linear regression models with random slopes. A subset of 46 individuals had LTL measured over time, and we assessed the association of change in LTL with change in EDSS with mixed effects models in this subset.

Results Included were 356 women and 160 men (mean age 43 years, median disease duration 6 years, median EDSS 1.5 (range 0-7)). In analyses adjusted for age, disease duration and sex, for every 1 standard deviation (SD) unit lower LTL, EDSS was 0.25 units higher (95% CI 0.12-0.38, p<0.001) and total brain volume was 6.75 mm³lower (0.09-13.41, p=0.047) at baseline. In longitudinal adjusted analyses, those with lower baseline LTL consistently had higher EDSS and lower brain volumes over time. In adjusted analysis of the subset, change in LTL was predictive of change in EDSS over 10 years: for every 1 SD unit decrease in LTL, EDSS was 0.31 units higher (0.07-0.55, p=0.013).

Conclusions Shorter telomere length was associated with disability after adjustment for chronological age, suggesting biological aging may contribute to neurological injury in MS. Targeting aging-related mechanisms may be a potential therapeutic strategy.

Authors/Disclosures
Kristen M. Krysko, MD (St. Michael's Hospital) PRESENTER	Dr. Krysko has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Krysko has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Krysko has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Krysko has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Krysko has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Krysko has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. The institution of Dr. Krysko has received research support from MS Society of Canda. The institution of Dr. Krysko has received research support from Roche.
Roland G. Henry, PhD (University of California, San Francisco)	Dr. Henry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MEDDAY. Dr. Henry has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Henry has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Henry has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi/Genzyme.
Bruce A. Cree, MD, PhD, MAS, FAAN (UCSF, Multiple Sclerosis Center)	The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Autobahn. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avotres. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Horizon. Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neuron23. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Pharma. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal/Sandoz. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kyverna. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic AG. The institution of Dr. Cree has received research support from Genentech. The institution of Dr. Cree has received research support from Kyverna. Dr. Cree has received publishing royalties from a publication relating to health care.
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Refujia Gomez	Refujia Gomez has nothing to disclose.
Carolyn J. Bevan, MD (Jesse Brown VAMC)	Dr. Bevan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Bevan has received intellectual property interests from a discovery or technology relating to health care.
Dana Smith, Exhibito	No disclosure on file
William Stern	No disclosure on file
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Stephen L. Hauser, MD (UCSF Weill Institute for Neurosciences)	Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NGM Bio. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BD. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pheno Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nurix Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gilead. Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Accure. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alector. Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Annexon. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hinge Therapeutics. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Neurona. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Roche that is relevant to AAN interests or activities. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Novartis that is relevant to AAN interests or activities.
Jorge Oksenberg, MD (UCSF)	No disclosure on file
Jennifer Graves, MD, PhD (UCSD)	Dr. Graves has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Graves has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Graves has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for MSJ. The institution of Dr. Graves has received research support from Octave. The institution of Dr. Graves has received research support from Sanofi. The institution of Dr. Graves has received research support from EMD Serono.