A multi-center screening trial of rasagiline in patients with amyotrophic lateral sclerosis: Possible mitochondrial biomarker target engagement

Rasagiline, a monoamine oxidase B inhibitor, slowed disease progression in the SOD1 mouse, and in a case series of patients with amyotrophic lateral sclerosis (ALS). Here we determine whether rasagiline is safe and effective in ALS compared to historical placebo controls, and whether it alters mitoc...

Full description

Saved in:
Bibliographic Details
Published in:Amyotrophic lateral sclerosis and frontotemporal degeneration 2015-08, Vol.16 (5-6), p.345-352
Main Authors: Macchi, Zachary, Wang, Yunxia, Moore, Dan, Katz, Jonathan, Saperstein, David, Walk, David, Simpson, Ericka, Genge, Angela, Bertorini, Tulio, Fernandes, J. Americo, Swenson, Andrea, Elman, Lauren, Dimachkie, Mazen, Herbelin, Laura, Miller, Joann, Lu, Jianghua, Wilkins, Heather, Swerdlow, Russell H., Statland, Jeffrey, Barohn, Richard
Format: Article
Language:English
Subjects:
Aged
Amyotrophic Lateral Sclerosis - drug therapy
apoptosis
Apoptosis - drug effects
bcl-2-Associated X Protein - metabolism
Biomarker
clinical trials
Female
Humans
Indans - therapeutic use
Male
Membrane Potential, Mitochondrial - drug effects
Middle Aged
mitochondria
Neuroprotective Agents - therapeutic use
Oxidative Stress - drug effects
Proto-Oncogene Proteins c-bcl-2 - metabolism
rasagiline
Retrospective Studies
Statistics, Nonparametric
Time Factors
Treatment Outcome
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Rasagiline, a monoamine oxidase B inhibitor, slowed disease progression in the SOD1 mouse, and in a case series of patients with amyotrophic lateral sclerosis (ALS). Here we determine whether rasagiline is safe and effective in ALS compared to historical placebo controls, and whether it alters mitochondrial biomarkers. We performed a prospective open-label, multicenter screening trial of 36 ALS patients treated with 2 mg oral rasagiline daily for 12 months. Outcomes included the slope of deterioration of the revised ALS Functional Rating Scale (ALSFRS-R), adverse event monitoring, time to treatment failure, and exploratory biomarkers. Participants experienced no serious drug-related adverse events, and the most common adverse event was nausea (11.1%). Rasagiline did not improve the rate of decline in the ALSFRS-R; however, differences in symptom duration compared to historical placebo controls differentially affected ALSFRS-R slope estimates. Rasagiline changed biomarkers over 12 months, such that the mitochondrial membrane potential increased (JC-1 red/green fluorescent ratio 1.92, p = 0.0001) and apoptosis markers decreased (Bcl-2/Bax ratio 0.24, p < 0.0001). In conclusion, engagement of exploratory biomarkers and questions about comparability of baseline characteristics lead us to recommend a further placebo-controlled trial.
ISSN:2167-8421
2167-9223
DOI:10.3109/21678421.2015.1026826