A study published in the Journal of Neuroscience and supported by The ALS Association shows that motor neurons in the brain may offer an unexpected new target for therapy in ALS.
While the motor neurons that extend from the brain into the spinal cord (so-called “upper” motor neurons) have been known to be involved in the disease, previous work in mouse models has focused primarily on “lower” motor neurons, those that extend from the spinal cord to the muscle. Recent research on upper motor neurons by other Association-funded scientists, including Hande Ozdinler, Ph.D., of Northwestern University, has led to progress in better understanding this important and unique group of neurons, and their contributions to the ALS disease process.
In this new study, Association-funded lead researcher Gretchen Thomsen, Ph.D., along with principal investigator Clive Svendsen, Ph.D., examined the effect of the disease-causing mutant SOD1 protein in a rat model of ALS. The researchers discovered that reducing the level of mutant SOD1 in upper motor neurons delayed disease onset, prolonged survival, and enhanced the survival of lower motor neurons, even though the lower motor neurons continued to have harmful levels of the protein.
The results suggest that the survival of lower motor neurons depends in part on upper motor neurons and that therapies targeting upper motor neurons may be especially helpful.
“These results point toward the motor neurons in the brain as a significant target for therapy development,” said Lucie Bruijn, Ph.D., M.B.A., Chief Scientist for The Association. “They also point out the importance of studying multiple disease models, each of which may provide unique insights into the causes and treatment of ALS.”