Stopping ALS starts with knowing how it spreads

Amyotophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a devastating and fatal neurodegenerative condition that includes symptoms such as paralysis and loss of the ability to walk, talk, eat, and breathe. Although there is no cure for ALS, patients suffering from the disease may find hope in a recent discovery by researchers at the Vancouver Coastal Health Research Institute (VCHRI) about how it spreads within the body that could lead to revolutionary new immunotherapies.

“Our work identifies an important piece of the puzzle in determining how ALS is transmitted throughout the nervous system,” says lead investigator Dr. Neil Cashman, VCHRI researcher and University of British Columbia clinical neurologist and neuroscientist affiliated with the Djavad Mowafaghian Centre for Brain Health. “This discovery is a first step toward the development of targeted treatments that may stop progression of the disease.”

Characteristic to ALS is the degeneration and death of motor neurons, which in turn stops messages from reaching muscles, causing them to gradually weaken and atrophy. Eventually, the brain loses its ability to start and control voluntary movement.

Discoveries point to new therapeutic approach

In findings published earlier this year in Proceedings of the National Academy of Sciences, Dr. Cashman and his research team demonstrates that the SOD1 protein (superoxide dismutase 1), which has been shown to play a role in the ALS disease process, participates in a process called template-directed misfolding. This process is the coercion of one protein by another protein to change shape and accumulate in large complexes and is central to the progressive spread of ALS.

“Our work has identified a specific molecular target, which when manipulated halts the conversion of the SOD1 protein to a misfolded, disease-causing form,” explains Dr. 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 Centre.

“These discoveries in cell culture point to a rational therapeutic approach to all types of ALS.”

Dr. Cashman and his team’s next plans are to determine how “seeding” of misfolded SOD1 first occurs and push forward with human antibodies into models that will capture the cell-to-cell spread of misfolded Wild Type (WT) SOD1. While programs are currently under development for SOD1 immunotherapies, clinical trials for this novel treatment modality are likely a few years away.