Abstract Details

Title Elongator Protein 1 as a Biomarker of Disease Severity in Familial Dysautonomia

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S9 - Autonomic Disorders (11:51 AM-12:03 PM)

Poster/Presentation
Number 004

Background Familial dysautonomia (FD) is an inherited sensory and autonomic neuropathy with significant phenotypic variability and decreased levels of elongator protein 1 (ELP1). We hypothesize that patients with higher levels of normal wild-type ELP1 would present a milder phenotype.

Objective To evaluate whether blood ELP1 levels correlate with sensory and motor nerve function and could serve as a biomarker.

Design/Methods We conducted a retrospective cross-sectional study of 125 participants, including 59 FD patients homozygous for the founder mutation and 66 heterozygous carriers. We developed a specific radioimmunoassay (RIA) for measuring ELP1 levels in blood. Sensory function was assessed using quantitative sensory testing (QST) and nerve conduction velocities (NCV). We measured cold, warm, and vibration detection thresholds and ELP1 levels in 120 FD patients, with repeat ELP1 levels taken one year later in a subset of 22 participants to assess reproducibility.

Results The average ELP1 levels in FD patients were significantly lower than in carriers (244 ± 75 vs. 2210 ± 1031 pg/ml, p < 0.001). Higher ELP1 levels were significantly correlated with lower sensory thresholds for warm (r = 0.366, p = 0.04), cold (r = 0.496, p = 0.01), and vibration thresholds (r = 0.550, p < 0.001) and with higher amplitudes of sensory nerve action potential (SNAP) in the median nerve (r = 0.550, p < 0.001), suggesting a role for ELP1 in preserving sensory nerve integrity. No correlation was found between motor conduction velocities and ELP1 levels, which may reflect the differential impact of FD on sensory versus motor neurons. Test-retest reproducibility of ELP1 measurements demonstrated high reliability (R² = 0.827, p < 0.001).

Conclusions Blood ELP1 levels appear stable over time and are significantly associated with sensory nerve function in patients with FD, making ELP1 a potential biomarker for monitoring disease severity and a marker of target engagement in clinical trials.

Authors/Disclosures
Maria Alejandra Gonzalez Duarte, MD, FAAN (NYU Dysautonomia Center) PRESENTER	Dr. Gonzalez Duarte has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alnylam. Dr. Gonzalez Duarte has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astra Zeneca. Dr. Gonzalez Duarte has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alnylam . The institution of Dr. Gonzalez Duarte has received research support from Pfizer.
Lucy Norcliffe-Kaufmann, PhD	Prof. Norcliffe-Kaufmann has received personal compensation for serving as an employee of Theravance BioPharma. Prof. Norcliffe-Kaufmann has received personal compensation for serving as an employee of 23andMe.
Kaia L. Dalamo, NP	Dr. Dalamo has nothing to disclose.
Maria Cotrina, PhD	Mrs. Cotrina has nothing to disclose.
Joel Gutierrez, MD (Cuban Institute of Neurology & Neurosurgery)	Dr. Gutierrez has nothing to disclose.
Horacio C. Kaufmann, MD, FAAN (NYU Langone Health - NYU Dysautonomia Center)	Dr. Kaufmann has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Theravance. Dr. Kaufmann has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Parexel. Dr. Kaufmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva Pharmaceuticals. Dr. Kaufmann has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Curasen Therapeutics. Dr. Kaufmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Kaufmann has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda Pharmaceuticals. Dr. Kaufmann 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 Spinger. The institution of Dr. Kaufmann has received research support from Biogen. The institution of Dr. Kaufmann has received research support from Vaxxinity. Dr. Kaufmann has received publishing royalties from a publication relating to health care.

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