Researchers in London have shown that mutation in a gene that causes 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. The study, published in the online scientific journal Neuron, is supported by The ALS Association’s Translational Research Advancing Therapies (TREAT ALS™) program.
“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.
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.
Researchers who led the study are 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 featured in the same issue of Neuron, researchers in Tennessee showed that VCP mutations also impair clearance of damaged mitochondria.
“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.
The Association’s Translational Research Advancing Therapies (TREAT ALS™) program funds a diverse portfolio of research at leading institutions around the globe. 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.