Abstract Details

Title Cross-sectional and Longitudinal Natural History of CLN3 Disease Progression

Topic Child Neurology and Developmental Neurology

Presentation(s) S27 - Child Neurology and Developmental Neurology: Neurogenetics: Translating Knowledge to Therapy (2:12 PM-2:24 PM)

Poster/Presentation
Number 007

Objective

To quantify the relationship between symptom severity and age in CLN3 disease using both cross-sectional and longitudinal analyses.

Background

CLN3 disease (Juvenile Batten Disease) is a neurodegenerative disease beginning in early childhood and progressing until death in the third decade of life.

Design/Methods

Participants were evaluated using the Unified Batten Disease Rating Scale (UBDRS), a disease-specific rating scale with four subscales: physical, seizure, behavioral, and functional capability. The most recent evaluation for each participant, including those with only a single time point, was used to perform cross-sectional analyses. For individuals with multiple time points, longitudinal analyses were performed accounting for the effect of multiple within-subject evaluations.

Results

We analyzed data from 126 unique individuals with a total of 380 evaluations. 47 individuals were evaluated at a single time point; 79 individuals had serial evaluations with up to 15 assessments per individual. In both cross-sectional and longitudinal analyses, the physical, seizure, and functional capability scores correlated with age. The behavior score did not correlate with age. The annual rate of physical progression was 3.02 ± 0.24 (slope ± SE) points (cross-sectional) and 3.11 ± 0.28 points (longitudinal). The annual rate of seizure progression was 0.53 ± 0.10 points (cross-sectional) and 0.59 ± 0.08 points (longitudinal). The annual rate of functional capability change was 0.53 ± 0.06 points (cross-sectional) and 0.60 ± 0.04 points (longitudinal).

Conclusions Our data provide a global assessment of CLN3 disease severity and show a nearly linear rate of relentless progression after onset. Cross-sectional and longitudinal analyses yielded similar results, supporting the combination of cross-sectional with longitudinal approaches to increase sample size in this rare disease. They also suggest the potential for combining such data as a baseline for future clinical trials in CLN3 disease. Used in combination with symptom age-at-onset, these data provide a comprehensive picture of CLN3 disease natural history.

Authors/Disclosures
Margaux C. Masten, Undergraduate PRESENTER	The institution of Miss Masten has received research support from AAN. The institution of Miss Masten has received research support from Neurogene. The institution of Miss Masten has received research support from Amicus. The institution of Miss Masten has received research support from Beyond Batten Disease Foundation. The institution of Miss Masten has received research support from NIH.
Jennifer A. Vermilion, MD (University of Rochester)	The institution of Dr. Vermilion has received research support from Centers for Disease Control. The institution of Dr. Vermilion has received research support from Emalex Biosciences. The institution of Dr. Vermilion has received research support from Biomarin. The institution of Dr. Vermilion has received research support from Neurogene, Inc. Dr. Vermilion has received personal compensation in the range of $500-$4,999 for serving as a Invited Speaker with Tourette Association of America. Dr. Vermilion has received personal compensation in the range of $500-$4,999 for serving as a Invited Speaker with Centers for Disease Control and Prevention and American Academy of Pediatrics.
Heather Adams	The institution of Heather Adams has received research support from Current: NIH; Past: Abeona; Batten Research Alliance; American University Centers on Disabilities. An immediate family member of Heather Adams has received publishing royalties from a publication relating to health care. Heather Adams has received personal compensation in the range of $500-$4,999 for serving as a Consultant with Critical Path Institute.
Amy Vierhile, NP, DNP (University of Rochester Medical Center)	Ms. Vierhile has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Greenwich Biosciences.
Frederick J. Marshall, MD (University of Rochester)	The institution of Dr. Marshall has received research support from CHDI. The institution of Dr. Marshall has received research support from Huntington Study Group.
	No disclosure on file
Jonathan W. Mink, MD, PhD, FAAN	The institution of Dr. Mink has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus. The institution of Dr. Mink has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurogene. Dr. Mink has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TEVA. Dr. Mink has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC Therapeutics. Dr. Mink has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Applied Therapeutics. Dr. Mink has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. The institution of Dr. Mink has received research support from Neurogene. The institution of Dr. Mink has received research support from NIH. Dr. Mink has received publishing royalties from a publication relating to health care. Dr. Mink has received personal compensation in the range of $500-$4,999 for serving as a Member, Study Section with NINDS.
Erika F. Augustine, MD, FAAN (Kennedy Krieger Institute)	The institution of Dr. Augustine has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Latus Bio. Dr. Augustine has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC Therapeutics. Dr. Augustine 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 American Board of Psychiatry and Neurology. Dr. Augustine has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Medlink. Dr. Augustine has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Annals of Neurology. The institution of Dr. Augustine has received research support from NIH. The institution of Dr. Augustine has received research support from Beyond Batten Disease Foundation. Dr. Augustine has received publishing royalties from a publication relating to health care. Dr. Augustine has a non-compensated relationship as a Member, Board of Directors with American Brain Foundation that is relevant to AAN interests or activities.

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