Abstract Details

Title Whole Blood Transcriptional Profiling of Sporadic Amyotrophic Lateral Sclerosis Patients Identifies a Sub-Population with an Inflammatory Component

Topic Anterior Horn

Presentation(s) P02 - (-)

Poster/Presentation
Number 175

Objective

Background BACKGROUND: sALS is a progressive neurodegenerative disease with a still incompletely understood etiology. Recent animal and pathological studies have suggested a role of neuroinflammation, and therefore we have investigated the possibility of finding disease-specific transcriptional changes in peripheral blood from sALS donors. Characterization of transcriptional profiles can often help identify different factors involved in disease pathology and suggest new therapeutic interventions.

Design/Methods DESIGN/METHODS: RNA from 23 untreated sALS and 19 matched healthy subjects was derived from whole peripheral blood (Tempus) and analyzed by microarray (Illumina HT12v4) with traditional hierarchical clustering and novel transcriptional module techniques (Chaussabel et al 2008 Immunity 29:150). Subjects were clinically characterized by an experienced ALS neurologist (DH) and were untreated at the time of blood sampling. sALS subjects were matched for age, gender, and ethnicity with healthy control subjects. Disease-specific pathways were derived from differentially expressed gene lists using Ingenuity Pathway Analysis (IPA) software.

Results RESULTS: Whole genome mRNA transcription profiling of sALS peripheral blood yielded approximately 1000 differentially over- or under-expressed genes that met specified stringency criteria compared to matched healthy controls. Of the top 25 canonical pathways identified (p=4e-05 to 8e-03), about half of the pathways involve aspects of inflammation, particularly innate immune processes. Other identified pathways include several non-inflammatory processes previously implicated in ALS. Modular analysis of individual sALS patients shows about half to overexpress transcriptional modules associated with interferon or inflammatory processes.

Conclusions CONCLUSIONS: Whole genome transcriptional analyses demonstrate the presence of an sALS sub-population characterized by the overexpression of interferon- and inflammation-related pathways. These findings could help in future development of diagnostic and therapeutic strategies in ALS.

Authors/Disclosures
Daragh Heitzman, MD, FAAN (Texas Neurology) PRESENTER	The institution of Dr. Heitzman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amylyx Pharmaceuticals. The institution of Dr. Heitzman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cytokinetics. The institution of Dr. Heitzman has received personal compensation in the range of $0-$499 for serving as a Consultant for MMIT . The institution of Dr. Heitzman has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Amylyx Pharmaceuticals. The institution of Dr. Heitzman has received research support from Muscular Dystrophy Association. The institution of Dr. Heitzman has received research support from Amylyx Pharmaceuticals. The institution of Dr. Heitzman has received research support from Anelixis. The institution of Dr. Heitzman has received research support from Cytokinetics. The institution of Dr. Heitzman has received research support from Mitsubishi - MT. The institution of Dr. Heitzman has received research support from Healey Platform Trial.
	No disclosure on file
	No disclosure on file
J. Theodore Phillips, MD, PhD, FAAN	No disclosure on file
Gregory A. Jicha, MD, PhD (University of Kentucky College of Medicine)	Dr. Jicha has nothing to disclose.
Robert A. Bermel, MD, FAAN (Cleveland Clinic)	Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi/Genzyme. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech/Roche. Dr. Bermel has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Bermel has received research support from Biogen. The institution of Dr. Bermel has received research support from Roche. The institution of Dr. Bermel has received research support from Novartis. Dr. Bermel has received intellectual property interests from a discovery or technology relating to health care.

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