The study reported in Science today (Feb. 27) points to a common cellular deficiency in the fatal neurological disorder, said Teepu Siddique, M.D., Les Turner ALS Foundation/Herbert C. Wenske Foundation Professor in the Davee Department of Neurology and Clinical Neurosciences and Department of Cell and Molecular Biology and Director of the Division of Neuromuscular Medicine at the Feinberg School.
The new research is part of a national collaboration directed by Siddique, the principal investigator for the "Genetics of ALS" project funded at Feinberg by the National Institutes of Health.
Earlier research by Siddique and colleagues extended the genetic knowledge of familial (inherited) ALS by identifying the first and second ALS genes (the SOD1 gene in 1993 and the ALSIN gene in 2001), in addition to identifying loci on chromosomes 9, 15, 16, and X.
The study published today discovered aFUS/TLS gene mutations in ALS families collected through efforts of the NIH-funded multi-centre project and included among others a large Italian family previously studied by Siddique and Cortelli.
ALS affects the motor neurons in the central nervous system. As motor neurons die, the brain's ability to send signals to the body's muscles is compromised. This leads to loss of voluntary muscle movement, paralysis and eventually death from respiratory failure. The cause of most cases of ALS is not known.
"The purpose of this national study is to understand what triggers the death of motor neurons in order to find new cellular models of ALS, with the ultimate goal of advancing research that leads to a treatment for this fatal disease," Siddique said. "Approximately 10 percent of ALS cases are inherited."
"The discovery of this gene mutation shows new kinds of molecular defects that damage motor neurons and it implicates defective pathways previously identified in other genetic forms of ALS," said Siddique.