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Abstract Details

CSF biomarkers evaluated by principal component analysis in a NurOwn Phase 3 clinical trial
Neuromuscular and Clinical Neurophysiology (EMG)
P1 - Poster Session 1 (9:00 AM-5:00 PM)
400

To evaluate NurOwn and Placebo on CSF biomarkers across pathways of neuroinflammation, neurodegeneration and neuroprotection using principal component analysis (PCA).

MSC-NTF cells (NurOwn®) are autologous bone-marrow derived mesenchymal stem cells (MSC) induced to secrete high levels of neurotrophic factors (NTFs). MSC-NTF cells were administered in three bimonthly intrathecal injections to ALS participants in a Phase 3 double-blind, placebo-controlled trial (NCT03280056).

CSF was collected at 7 time points and 37 CSF biomarkers were pre-specified, with the primary pathway identified prior to unblinding.  PCA is a statistical procedure that allows important information to be extracted from data and expressed in the form of a summary indices, or principal components (PC). 

PCA provided an effective summary of the treatment effects across biomarker categories with the treatment effect on neurodegeneration summarized through 1 PC and neuroinflammation and neuroprotection through 2 PC.  The PCA reveals that neuroprotection is increased across the trial and remains high for NurOwn compared to Placebo.  Analysis of the PC for neurodegeneration and neuroinflammation suggest inflammatory and neurodegeneration levels are lowered for NurOwn compared to Placebo.  Across all three biomarker categories, the placebo group PC remain stable or slightly decrease.  Statistical analysis on each of the PC independently suggests that NurOwn has a strong influence on multiple cellular pathways with the strongest effects on neuroprotection and neuroinflammation domains.  These analyses are consistent with the changes observed on individual biomarkers.

ALS is a complex disease in which neurodegeneration, neuroinflammation and failure of intrinsic neuroprotective mechanisms may play an important role1.  NurOwn treatment resulted in consistent longitudinal changes in specific CSF neurodegenerative, neuroinflammatory, and neuroprotection biomarkers and within biomarker categories as identified by PCA analysis.

PCA analysis of NurOwn treatment effects across biomarker categories contributes to the understanding of its mechanism of action in ALS.

Authors/Disclosures
James D. Berry, MD MPH (Massachusetts General Hospital)
PRESENTER 		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.
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.
Robert H. Brown, Jr., MD, DPhil (Univ of Massachusetts Medical School) Dr. Brown has received personal compensation for serving as an employee of ApicBio. Dr. Brown has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for ApicBio. Dr. Brown 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 Warren Alpert Foundation. Dr. Brown has stock in ApicBio. Dr. Brown has stock in Amylx. Dr. Brown has stock in Imstar. The institution of Dr. Brown has received research support from Angel Fund for ALS Research. The institution of Dr. Brown has received research support from ALS Association. The institution of Dr. Brown has received research support from ALSOne. The institution of Dr. Brown has received research support from NINDS. The institution of Dr. Brown has received research support from ALS Finding A Cure. Dr. Brown has received publishing royalties from a publication relating to health care.
Revital Aricha Revital Aricha has nothing to disclose.
No disclosure on file
Anthony J. Windebank, MD, FAAN (Mayo Clinic) Dr. Windebank has nothing to disclose.
Nathan P. Staff, MD, PhD, FAAN (Mayo Clinic) Dr. Staff has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Stem Cell Research & Therapy. Dr. Staff has received research support from National Institutes of Health.
Namita Goyal, MD, FAAN (University of California, Irvine) Dr. Goyal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Goyal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Annexon. Dr. Goyal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abcuro. Dr. Goyal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. Dr. Goyal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Souffle. Dr. Goyal has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for CSL Behring. Dr. Goyal has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Argenx. Dr. Goyal has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Amgen. The institution of Dr. Goyal has received research support from Fulcrum. The institution of Dr. Goyal has received research support from Healey Platform. The institution of Dr. Goyal has received research support from Medicinova. The institution of Dr. Goyal has received research support from Transposon. The institution of Dr. Goyal has received research support from Abcuro. The institution of Dr. Goyal has received research support from Calico. The institution of Dr. Goyal has received research support from Clene. The institution of Dr. Goyal has received research support from Janssen. The institution of Dr. Goyal has received research support from PepGen. The institution of Dr. Goyal has received research support from PTC. The institution of Dr. Goyal has received research support from Roche. The institution of Dr. Goyal has received research support from Sanofi. The institution of Dr. Goyal has received research support from Prilenia. The institution of Dr. Goyal has received research support from RAPA. The institution of Dr. Goyal has received research support from Avidity. Dr. Goyal has received publishing royalties from a publication relating to health care.
Robert G. Miller, MD (Dept Of Neurology, CA Pacific) The institution of Dr. Miller has received research support from Nurown.
Jonathan S. Katz, MD (CPMC) Dr. Katz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Katz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Katz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Calico. Dr. Katz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CSL Behring. Dr. Katz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenyx. Dr. Katz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylyx. Dr. Katz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Denali. Dr. Katz has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Griffols. Dr. Katz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Katz has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion.
Matthew Burford, MD (Cedars-Sinai Medical Center) The institution of Dr. Burford has received research support from Brainstorm Cell Therapeutics. The institution of Dr. Burford has received research support from Pharnext Inc.
No disclosure on file
Chaim Lebovits (BrainStorm Cell Therapeutics) No disclosure on file
Yael Gothelf Yael Gothelf, 18041 has received personal compensation for serving as an employee of Brainstorm Cell Therapeutics.
No disclosure on file
Munish Mehra No disclosure on file
Stacy Lindborg, PhD Dr. Lindborg has received personal compensation for serving as an employee of Brainstorm Cell Therapeutics. Dr. Lindborg has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Celsion.