The ALS Association

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Researchers Discover Cell-to-Cell Spread of Misfolded ALS Protein in Cell Model

February 25, 2014

In a study published in the Proceedings of the American Academy of Sciences, researchers at the University of British Columbia in Vancouver, Canada have found a potential new mechanism for the spread of ALS disease pathology in cell models. The results may point to possible new therapeutic strategies.

Mutations in the gene for superoxide dismutase 1 (SOD1) are a cause of about 20 percent of familial or inherited ALS. Misfolded mutant SOD1 protein is believed to contribute to the disease process in those carrying the mutation, yet the role of misfolded non-mutant protein in the disease is unclear. Researchers in this study, who were led by Neil Cashman, M.D., of the University of British Columbia, Vancouver, Canada, showed that both misfolded mutant protein and misfolded normal protein can be released by one cell and picked up by another cell. The uptake of misfolded protein can lead to misfolding of normal protein in the cell that takes it in, propagating the misfolding process from cell to cell. That cell-to-cell transmission could be reduced by antibodies against the SOD1 protein.

“These results are intriguing and potentially important in understanding the ALS disease process,” said Lucie Bruijn, Ph.D., MBA, Chief Scientist for The Association. “If the spread from cell to cell seen in this cell model also occurs in people with ALS, it could help explain the progression of the disease after it begins and point to blocking that spread as a new and important treatment strategy, including for individuals with non-SOD1-related ALS. However, more work will need to be done to determine whether misfolded SOD1 does in fact move from cell to cell in humans and whether this process contributes to the pattern of disease progression we see. Answering these important questions takes on new urgency with the publication of this study.”

One approach to therapy would be to treat with antibodies against misfolded proteins. Several groups have shown that this strategy has benefit in the SOD1 mouse model of ALS. Investigators Janice Robertson, Ph.D., of the University of Toronto, Toronto, Canada and Joan Coates, University of Missouri, Mo., are testing this approach in a canine model of the disease in an Association-funded study.

Read the press release.

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