Abstract Details

Title Microglial Activation in People with Amyotrophic Lateral Sclerosis

Topic Anterior Horn

Presentation(s) P06 - (-)

Poster/Presentation
Number 132

Objective

Background BACKGROUND: Activated microglia are increased in postmortem tissue from patients with ALS compared to healthy controls. In addition, activated microglia are detected early near motor neurons of the SOD1G93A transgenic mouse model of ALS at 39 days of life. Numerous Positron Emission Tomography (PET) ligands have been developed to image activated immune cells. We are reporting on our ongoing study of imaging microglial activation in people with ALS using [11C]-PBR28. This is a new radiotracer that binds to translocator protein (18Da, TSPO) that is highly expressed on activated microglia.

Design/Methods DESIGN/METHODS: Five subjects with ALS and five age-matched healthy volunteers will be scanned at the Martinos Center for Biomedical Imaging at Massachusetts General Hospital. All eligible subjects will undergo IV placement for [11C]-PBR28 administration and arterial line placement for full PET quantitative analysis. Voxel-wise and ROI-average binding of [11C]-PBR28 will be measured by calculating total distribution volume (Vt) using a Logan plot and metabolite-corrected arterial input function. Cortical and subcortical ROIs will be defined by automated segmentation of high-resolution structural MR images. Clinical measures include disease duration, ALSFRS-R, vital capacity, reflexes, and hand held dynamometry.

Results RESULTS: This is a work in progress. At the time of abstract preparation, three ALS subjects had completed the PBR28-PET protocol. Quantitative analysis was completed on one ALS subject. [11C]-PBR28 bindings is 30% increased in the motor cortices compared to adjacent brain regions. This result is in line with previously published pathological findings of increased microglia near motor neurons in ALS. More subjects with ALS are scheduled for scanning and further data analysis is underway.

Conclusions CONCLUSIONS: Our preliminary findings suggest that [11C]-PBR28 uptake is increased in the motor cortex in people with ALS.

Authors/Disclosures
Robert J. Lawson (Massachusetts General Hopital) PRESENTER	No disclosure on file
	No disclosure on file
Darlene E. Sawicki, RN, NP (Massachusetts General Hospital)	No disclosure on file
James D. Berry, MD MPH (Massachusetts General Hospital)	Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Clene Nanomedicine. Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MT Pharma Holdings of America. Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Regeneron. Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MTPA. Dr. Berry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Berry has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Berry has stock in ReactNeuro. The institution of Dr. Berry has received research support from Biogen. The institution of Dr. Berry has received research support from MT Pharma of America. The institution of Dr. Berry has received research support from Rapa Therapeutics. The institution of Dr. Berry has received research support from Brainstorm Cell Therapeutics. The institution of Dr. Berry has received research support from Alexion. The institution of Dr. Berry has received research support from nQ Medical. The institution of Dr. Berry has received research support from ALSA. The institution of Dr. Berry has received research support from MDA. The institution of Dr. Berry has received research support from Amylyx. The institution of Dr. Berry has received research support from Transposon. Dr. Berry has a non-compensated relationship as a Scientific Advisor with Everything ALS that is relevant to AAN interests or activities.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Emily A. Johnson	No disclosure on file
	No disclosure on file
	No disclosure on file
Bruce R. Rosen, MD (Massachusetts General Hosp.)	No disclosure on file
Merit E. Cudkowicz, MD, MSC, FAAN (Massachusetts General Hospital)	Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for biogen. Dr. Cudkowicz has received personal compensation in the range of $0-$499 for serving as a Consultant for cytokinetics. Dr. Cudkowicz has received personal compensation in the range of $0-$499 for serving as a Consultant for immunitypharm. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for transposon. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Quralis. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Regeneron. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for vectorY. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for inflectis. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for novartis. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ono. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for otsuka. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for coya. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ac immune. Dr. Cudkowicz has received personal compensation in the range of $0-$499 for serving as a Consultant for pontifax. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Inflectis. Dr. Cudkowicz has received personal compensation in the range of $0-$499 for serving as a Consultant for ab science. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for aclipse. Dr. Cudkowicz has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Locust Walk. Dr. Cudkowicz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pasithea. Dr. Cudkowicz has received personal compensation in the range of $50,000-$99,999 for serving as an officer or member of the Board of Directors for Praxis Precision Medicine. Dr. Cudkowicz 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. Cudkowicz has received research support from NINDS. The institution of Dr. Cudkowicz has received research support from ALSFAC. The institution of Dr. Cudkowicz has received research support from UCB ra. The institution of Dr. Cudkowicz has received research support from Biohaven. The institution of Dr. Cudkowicz has received research support from Clene nanomedicine. The institution of Dr. Cudkowicz has received research support from prilenia. The institution of Dr. Cudkowicz has received research support from ALS one. The institution of Dr. Cudkowicz has received research support from Seelos. The institution of Dr. Cudkowicz has received research support from Calico. The institution of Dr. Cudkowicz has received research support from denali. The institution of Dr. Cudkowicz has received research support from ITB. The institution of Dr. Cudkowicz has received research support from PharmAust. The institution of Dr. Cudkowicz has received research support from woolsley. Dr. Cudkowicz has received research support from lilly. The institution of Dr. Cudkowicz has received research support from J& J. Dr. Cudkowicz has received publishing royalties from a publication relating to health care.
Nazem Atassi, MD	Dr. Atassi has received personal compensation for serving as an employee of Sanofi. Dr. Atassi has stock in Sanofi.

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