June 25, 2009 

Scientists Discover Faster Protein Aggregation
Means Faster Disease Progression in ALS

A team of researchers have discovered that ALS progresses faster in patients whose gene mutations cause faster clumping of the SOD1 protein, linked to approximately 2 percent of all ALS cases.  Aggregation or clumping of the SOD1 protein is believed to be a crucial step in the disease process. 

Clumping of the mutant SOD1 protein has been observed in ALS patients and animal models of the disease.  More than 140 SOD1 mutations are known and different mutations cause different rates of progression.  To see whether there is a link between how fast the protein clumps and how fast the disease progresses, researchers in Florida, Texas and Sweden examined the aggregation rates of over 30 different proteins and compared them to the rate of disease progression in patients carrying each mutation. 

“We found that the inherent aggregation propensity is related to the duration of disease in people with ALS,” said lead author Mercedes Prudencio, a graduate student at the University of Florida at Gainesville, working with ALS Association-funded researcher David Borchelt, Ph.D., also of Gainesville and Peter Andersen, M.D., of Umea University in Sweden. 

The finding suggests that aggregated proteins may elude normal cellular “housecleaning” methods, or their formation is heightened by stress conditions in the cell.  As people with ALS begin to experience symptoms, the buildup of protein is rapid and dramatic.  However, it is well established that significant damage to the nervous system occurs well before the patient has any symptoms. 

“By linking speed of aggregation with the rate of disease progression, this study tells us that interrupting aggregation with drugs is likely to lead to a viable treatment strategy.  If we can target drugs to stop the aggregation, we can stop the progression of ALS,” said Lucie Bruijn, Ph.D., senior vice president of Research and Development at The ALS Association.  The ALS Association is currently working with investigators at Northwestern University and Cambria Pharmaceuticals to develop compounds that do just this as part of the Translational Research Advancing Therapies for ALS (TREAT ALS).