Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a neurodegenerative disease that causes progressive weakness, disability, and death. Treatments are largely palliative. Using mice carrying the mutated form of the human SOD1 gene that causes inherited forms of ALS, however, Berislav Zlokovic and colleagues, at the University of Rochester Medical Center, Rochester, have now found that administration of the protein APC slows disease progression and extends survival. The authors therefore suggest that strategies designed to activate APC might be of benefit to patients with inherited, and possibly sporadic, ALS. However, in an accompanying commentary, Charles Esmon and Jonathan Glass warn that such an approach would not be without risks.
In the study, administration of both APC, whose main function is to prevent blood clotting, and APC analogs with a reduced ability to prevent blood clotting slowed disease progression in the mutant SOD1–expressing mice and extended their survival, even when the compounds were administered after disease onset. Further analysis indicated that these compounds were able to access the brain and that once there, they worked by decreasing expression of the mutant SOD1 in several cell types in the brain, including the nerve cells destroyed in individuals with ALS. This study therefore indicates that APC can have a neuroprotective effect in mouse models of inherited ALS.
TITLE: Activated protein C therapy slows ALS-like disease in mice by transcriptionally inhibiting SOD1 in motor neurons and microglia cells
AUTHOR CONTACT:
Berislav V. Zlokovic
University of Rochester Medical Center, Rochester, New York, USA.
Phone: (585) 273-3132; Fax: (585) 273-3133; E-mail: berislav_zlokovic@urmc.rochester.edu .
View this article at: http://www.jci.org/articles/view/38476?key=6a5479a67edd727312aa
ACCOMPANYING COMMENTARY
TITLE: The APCs of neuroprotection
AUTHOR CONTACT:
Charles T. Esmon
Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Phone: (405) 271-6474; Fax: (405) 271-2872; E-mail: Charles-Esmon@omrf.org .
View the PDF of this article at: https://www.the-jci.org/article.php?id=40682
Journal of Clinical Investigation