Abstract Details

Title A Multicenter Screening Trial of the Safety and Efficacy of Rasagiline in People with ALS

Topic Anterior Horn

Presentation(s) S36 - (-)

Poster/Presentation
Number 006

Objective

Background Oxidative stress, mitochondrial dysfunction and apoptosis have been proposed as the cause of motor neuron death in ALS. Rasagiline, a monoamine oxidase B inhibitor, is FDA-approved for the symptomatic treatment of Parkinson disease. Rasagiline has demonstrated broad neuroprotective activities against a variety of neurotoxins in neuronal cell cultures and in the SOD mouse model of ALS. In vitro experiments indicate rasagiline stabilizes mitochondria under stress conditions.

Design/Methods Subjects are treated with rasagiline 2 mg daily for 12 months. The primary outcome measures are the number of adverse events and the change of the slope of ALS Functional Rating Scale-Revised (ALSFRS-R) over 12 months. Secondary outcome measures are the change in blood biomarkers including mitochondrial potentials in platelets, leukocytes Bcl/Bax ratio and indicators of apoptosis and oxidative stress following rasagiline administration.

Results Nine centers in the Western ALS (WALS) study group are participating in this study. Total 41 patients screened, 35 were enrolled and 30 remain on treatment with four dropouts due to either side effects (4), and one patient died. There were 18 men and 17 women, with a mean age at entry of 61 years (59-82), and mean disease duration was 1.5 years (0.5-3). 16 patients have been on rasagiline 2 mg for six months. The mean ALSFRS-R for these16 patient were: 37.2 baseline, 36,4 month 1, 32.5 month 6. Mean Jc-1 lymphocyte ratio was 0.46 relative fluorescence at baseline and 0.61 relative fluorescence at six months (P<0.02).

Conclusions Rasagiline appears to be safe in this ALS population. The change in mitochondrial membrane potentials indicates target engagement of the drug.

Authors/Disclosures
Yunxia Wang, MD, FAAN (KUMC) PRESENTER	Dr. Wang has nothing to disclose.
Douglas L. Arnold, MD, FAAN (Montreal Neurological Institute, McGill Univ)	Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Frequency Therapeutics. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Xfacto communications. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Find therapeutics. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Idorsia. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kiniksa. Dr. Arnold has stock in NeuroRx.
Dan Moore, PhD (California Pacific Medical Center)	No disclosure on file
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.
David S. Saperstein, MD (Center for Complex Neurology, EDS & POTS)	No disclosure on file
David Walk, MD, FAAN (Dept. of Neurology)	No disclosure on file
Ericka P. Greene, MD, FAAN (Methodist Hospital)	Dr. Greene has received personal compensation for serving as an employee of Argenx. Dr. Greene has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion, Inc. Dr. Greene has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylx. Dr. Greene has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB . Dr. Greene has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ionis . Dr. Greene has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for ABPN.
Angela L. Genge, MD (Mcgill University)	Dr. Genge has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for AL-S Pharma. Dr. Genge has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amylyx. Dr. Genge has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Quralis. Dr. Genge has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MTPA. Dr. Genge has received personal compensation in the range of $0-$499 for serving as a Consultant for WAVE. Dr. Genge has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for eikonizo. Dr. Genge has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for pepgen. Dr. Genge has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for rapa.
Tulio E. Bertorini, MD (Semmes Murphey Clinic)	Dr. Bertorini has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Bertorini has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for UCB. Dr. Bertorini has received publishing royalties from a publication relating to health care.
J. Americo M. Fernandes, Jr., MD, FAAN (University of Nebraska Medical Center)	Dr. Fernandes has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Columbia University. The institution of Dr. Fernandes has received research support from MGH philanthropy (Clene, Seelos, UCB, Biohaven, Prilenia, Denali Therapeutics, Calico Life Sciences. The institution of Dr. Fernandes has received research support from Columbia University. The institution of Dr. Fernandes has received research support from PTC Therapeutics. The institution of Dr. Fernandes has received research support from Clene.
Andrea J. Swenson, MD (University of Iowa Hospitals and Clinics)	An immediate family member of Dr. Swenson has received personal compensation for serving as an employee of IDT. Dr. Swenson has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. An immediate family member of Dr. Swenson has received stock or an ownership interest from IDT.
Russell H. Swerdlow, MD	No disclosure on file
Mazen M. Dimachkie, MD, FAAN (University of Kansas Medical Center)	Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Octapharma. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ArgenX. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Catalyst. Dr. Dimachkie has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Takeda. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medlink. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CSL Behring. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Janssen. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dianthus. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TACT / Treat NMD. Dr. Dimachkie has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Cabaletta Bio. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Clinical Neurological Society of America, Inc . Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ig Society, Inc. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abcuro. Dr. Dimachkie has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amicus. Dr. Dimachkie has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ipsen. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nuvig. Dr. Dimachkie has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Fortrea. The institution of Dr. Dimachkie has received research support from NIH. Dr. Dimachkie has received intellectual property interests from a discovery or technology relating to health care. Dr. Dimachkie has received intellectual property interests from a discovery or technology relating to health care. Dr. Dimachkie has received publishing royalties from a publication relating to health care.
April L. McVey, MD (April L. McVey, MD)	No disclosure on file
Laura Herbelin (KU Medical Center)	No disclosure on file
Zachary Macchi, MD (Intermountain Health)	The institution of Dr. Macchi has received research support from NIH/NIA.
Richard J. Barohn, MD, FAAN (University of Missouri)	Dr. Barohn has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for NuFactor. The institution of Dr. Barohn has received research support from FDA OPD R01. Dr. Barohn has received intellectual property interests from a discovery or technology relating to health care.

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