A group of investigators from the University of British Columbia and the Vancouver Coastal Health Research Institute have discovered a crucial link between prions and the neurodegenerative disease ALS (Amyotrophic Lateral Sclerosis), also known as Lou Gehrig's disease. This finding is considerable as it paves the way to new approaches to the treatment of ALS.

An important review published by the investigation team published this week in Proceedings of the National Academy of Sciences (PNAS), reveals that the SOD1 protein (superoxide dismutase 1), which has been shown to be involved in the process of ALS disease, exhibits prion-like properties. They discovered that SOD1 partakes in a process called template-directed misfolding. This term refers to the coercion of one protein by another protein to change shape and accumulate in large complexes in a similar way to the process underlying prion diseases.

These discoveries offer a molecular reason for the progressive spread of ALS through the nervous system, and draw attention to the key role of the propagation of misfolded proteins in the pathogenesis of neurodegenerative diseases, including ALS, Alzheimer's and Parkinson's.

Dr. Neil Cashman, Scientific Director of PrioNet Canada, Canada Research Chair in Neurodegeneration and Protein Misfolding at UBC, and academic director of the Vancouver Coastal Health ALS Center, explains:

"Our work has identified a specific molecular target, which when manipulated halts the conversion of the SOD1 protein to a misfolded, disease-causing form. This discovery is a first-step toward the development of targeted treatments that may stop progression of ALS."

Amyotrophic Lateral Sclerosis is a progressive neurmuscular disease in which nerve cells die, ultimately resulting in paralysis and death. In Canada, roughly 2,500 to 3000 individuals currently suffer with this fatal illness, and at present there is no effect treatment.

Dr. Leslie Grad, a co-first author of the project and current Manager of Scientific Programs at PrioNet Canada, said:

"For many years, ALS has remained a complex puzzle and we have found a key piece to help guide the research community to solutions. PrioNet is further exploring this discovery through newly-funded research project."

The investigation was conducted by Dr. Neil Cashman's lab at the Brain Research Center based at the University of British Columbia and the Vancouver Coastal Health Research Institute, together with investigators at the University of Alberta. The investigation was supported by PrioNet Canada and in part by Amorfix Life Sciences and the Canadian Institutes of Health Research.

Based in Vancouver, PrioNet Canada has gained international attention for scientific discoveries and risk management strategies directed at controlling prion diseases, and is now directing capacity into therapeutic solutions for prion-like diseases of aging, such as Alzheimer's, Parkinson's and ALS.

Written by Grace Rattue