Experimental Stroke Therapeutic Shows Promise for People with ALS

New research finds vascular damage in mice with ALS contributes to early development of the neurodegenerative disease, while repairing damage delays disease progression.

Keck School of Medicine of USC neuroscientists have unlocked a piece of the puzzle in the fight against Lou Gehrig’s disease, a debilitating neurological disorder that robs people of their motor skills. Their findings appear in the March 3, 2014, online edition of the Proceedings of the National Academy of Sciences of the United States of America, the official scientific journal of the U.S. National Academy of Sciences.

“We know that both people and transgenic rodents afflicted with this disease develop spontaneous breakdown of the blood-spinal cord barrier, but how these microscopic lesions affect the development of the disease has been unclear,” said Berislav V. Zlokovic, M.D., Ph.D., the study’s principal investigator and director of the Zilkha Neurogenetic Institute at USC. “In this study, we show that early motor neuron dysfunction related to the disease in mice is proportional to the degree of damage to the blood-spinal cord barrier and that restoring the integrity of the barrier delays motor neuron degeneration. We are hopeful that we can apply these findings to the corresponding disease mechanism in people.”

This is the neurovascular unit of a mouse spinal cord.
Fluorescent image shows cells of the neurovascular unit in the mouse spinal cord, which consists of motor neurons (green) and blood vessels containing pericytes (red) and endothelial cells (blue). Winkler et al. (2014) show that disruption of blood vessels accelerates injury of motor neurons in amyotrophic lateral sclerosis. Credit Ethan A. Winkler and Berislav V. Zlokovic/USC.

In this study, Zlokovic and colleagues found that an experimental drug now being studied in human stroke patients appears to protect the blood-spinal cord barrier’s integrity in mice and delay motor neuron impairment and degeneration. The drug, an activated protein C analog called 3K3A-APC, was developed by Zlokovic’s start-up biotechnology company, ZZ Biotech.

Lou Gehrig’s disease, also called amyotrophic lateral sclerosis, or ALS, attacks motor neurons, which are cells that control the muscles. The progressive degeneration of the motor neurons in ALS eventually leads to paralysis and difficulty breathing, eating and swallowing.

According to The ALS Association, approximately 15 people in the United States are diagnosed with ALS every day. It is estimated that as many as 30,000 Americans live with the disease. Most people who develop ALS are between the ages of 40 and 70, with an average age of 55 upon diagnosis. Life expectancy of an ALS patient averages about two to five years from the onset of symptoms.

ALS’s causes are not completely understood, and no cure has yet been found. Only one Food and Drug Administration-approved drug called riluzole has been shown to prolong life by two to three months. There are, however, devices and therapies that can manage the symptoms of the disease to help people maintain as much independence as possible and prolong survival.

Notes about this neuropharmacology and ALS research

The international research team included scientists from the The Scripps Research Institute, University of Rochester Medical Center, Sichuan University’s West China Hospital, and Ludwig Institute for Cancer Research at the University of California, San Diego. Grants from The ALS Association (1859) and National Institutes of Health (AG039452, AG23084, NS34467, HL031950, HL052246, NS27036) supported their research.

NeuroscienceNews.com would like to thank Alison Trinidad at USC for submitting this article to us.
Contact: Alison Trinidad – University of Southern California Health Sciences
Source: University of Southern California Health Sciences press release
Image Source: The image is credited to Ethan A. Winkler and Berislav V. Zlokovic/USC and is adapted from the press release.
Original Research: Full open access research for “Blood–spinal cord barrier disruption contributes to early motor-neuron degeneration in ALS-model mice” by Ethan A. Winkler, Jesse D. Sengillo, Abhay P. Sagare, Zhen Zhao, Qingyi Ma, Edward Zuniga, Yaoming Wang, Zhihui Zhong, John S. Sullivan, John H. Griffin, Don W. Cleveland, and Berislav V. Zlokovic in PNAS. Published online March 3 2014 doi:10.1073/pnas.1401595111

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