Study Finds Neurons and Support Cells Change Each Other for the Worse in Lou Gehrig's Disease

WASHINGTON, Feb. 4, 2013 /PRNewswire-USNewswire/ -- A study published in The Proceedings of the National Academy of Sciences USA has revealed that the disease process in amyotrophic lateral sclerosis (ALS) involves a complex genetic interplay between motor neurons and astrocytes. Motor neurons are the cells that die during the disease, leading to paralysis. Astrocytes normally support motor neurons but switch to the opposite role during disease progression. 

ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Eventually, people with ALS lose the ability to initiate and control muscle movement, which often leads to total paralysis and death within two to five years of diagnosis. There is no cure and no life-prolonging treatments for the disease. 

"These results strengthen the case that astrocytes are central to the ALS disease process," said Lucie Bruijn, Ph.D., Chief Scientist for The ALS Association. "Furthermore, the results are based on an exciting new disease model system, one that will allow us to test important hypotheses and search for new therapeutic targets."

Funded in part by The Greater New York Chapter of The ALS Association and the Alabama Chapter of The ALS Association, the study was performed by Hemali Phatnani, Ph.D., and colleagues and led by Tom Maniatis, Ph.D., from Columbia University Medical Center in New York in partnership with colleagues at the HudsonAlpha Institute for Biotechnology in Huntsville, Ala. The study was conducted in a cell culture model of ALS derived from embryonic stem cells and in mouse models of ALS.

In this research, normal and diseased motor neurons and astrocytes were cultured together in various combinations and then separately analyzed. The authors tracked changes in the two types of cells by carefully identifying the RNA each cell type produced. RNA is a genetic messenger molecule that indicates which genes the cell is using at any moment. It was not previously possible to simultaneously examine gene changes over time in motor neurons and astrocytes in the same experimental system. Tracking the two cell types at the same time allowed the investigators to observe how changes in each cell type influence changes in the other. The communication between neurons and astrocytes "is profoundly disrupted" by the disease process, the researchers concluded.

Cells communicate with each other by releasing molecules that bind to specific receptors on the surface of other cells. The authors found this normal communication system was disrupted in the disease, which resulted in a network of gene changes that reduced protective behaviors for both types of cells and increased harmful activity by the astrocytes. 

"This study points out several potential points for treatment intervention," Dr. Bruijn said, in order to prevent the loss of protective behavior or mitigate the harmful activity.

An important next step is to determine whether the harmful pathways identified in this model of ALS are also seen in other models and in the human disease. Finding the commonalities between the models and human ALS should provide the most robust targets for therapies. This goal was furthered by establishing a massive public gene expression database that can continue to be built and interrogated for "ALS disease signatures" in the future.

About The ALS Association
The ALS Association is the only national non-profit organization fighting Lou Gehrig's Disease on every front.  By leading the way in global research, providing assistance for people with ALS through a nationwide network of chapters, coordinating multidisciplinary care through certified clinical care centers, and fostering government partnerships, The Association builds hope and enhances quality of life while aggressively searching for new treatments and a cure.  For more information about The ALS Association, visit our website at www.alsa.org.

SOURCE The ALS Association