Study Funded by The ALS Association Finds ALS-causing Mutation Reduces Cellular Energy Supply

Mar 14, 2013, 15:03 ET from The ALS Association

WASHINGTON, March 14, 2013 /PRNewswire-USNewswire/ -- In research supported by The ALS Association and published in the online journal Neuron, scientists in London have shown that mutation in a gene that causes amyotrophic lateral sclerosis (ALS) reduces the energy supply in neurons and other cells—suggesting that the inability to produce sufficient quantities of energy is an important step in causing some cases of ALS.

ALS, also known as Lou Gehrig's Disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. The disease robs people of the ability to walk, to talk and even blink an eye.  It traps them inside a body they no longer can control and ultimately prevents them from breathing as it takes their life.  There is no known cause of the disease, although military veterans are approximately twice as likely to develop ALS as the general population.

"This discovery highlights the importance of energy to motor neurons and suggests that inability to produce sufficient quantities of it is an important step in causing some cases of ALS," said Lucie Bruijn, Ph.D., Chief Scientist for The Association. Motor neurons are the cell type that dies in the disease.

This new research found that mutations in a gene called VCP (for valosin-containing protein) affected the cell's energy factories, called mitochondria. ALS-causing mutations severely reduced the amount of ATP, an energy transfer molecule, made by the mitochondria. The reduction in ATP left the cells more vulnerable to stresses and increased their death. This is the first study to identify a potentially harmful activity caused by the gene mutation.

The research was led by Helene Plun-Favreau, Ph.D., and Andrey Abramov, Ph.D., both of the UCL Institute of Neurology at Queen Square in London. In a separate paper in the same issue of Neuron, researchers in Tennessee showed that VCP mutations also impair clearance of damaged mitochondria.

VCP mutations account for 1 percent to 2 percent of cases of familial ALS. VCP mutations are also responsible for diseases affecting muscle, bone, and the brain's frontal cortex, likely indicating the widespread effects of reduced energy production.

"By calling our attention to the effects of reduced energy production, this research strengthens the idea that supporting neurons in stress may be a valuable therapeutic strategy for ALS," Dr. Bruijn said.

Support of this research was made possible through The ALS Association's Translational Research Advancing Therapies (TREAT ALS™) program, which funds a diverse portfolio of research at leading institutions all over the world. Projects are selected through a peer review process and specifically focus on the most promising studies that we think have the highest potential to lead to treatments and a cure. As of January 2013, The ALS Association has more than 90 active research projects worth a total of $15.5 million.

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

SOURCE The ALS Association