Recognition that the mutations adversely impact regulation of RNA could lead to targeted therapy to correct the problem. The mutation’s location in the prion-like domain might also prove significant. Although the mutations in hnRNPA2B1 or hnRNPA1 appear to be rare, hundreds of other RNA-binding proteins have prion-like domains. Taylor said patients with unexplained neurodegenerative diseases may have mutations in these proteins.
Strong’s team is convinced ALS is a disorder of RNA metabolism. RNA is the intermediary or messenger between genes and the protein being made. This new protein appears to play a critical role. “Every time we look at a cell degenerating, this particular protein was deposited abnormally in the cell. It was a common denominator,” explains Strong, who is also the Dean of Schulich Medicine & Dentistry. “Working with Dr. Rob Hegele at Robarts, we found there was a genetic mutation in the gene coding for this protein. So it’s a huge discovery.”