Researchers at the University of Wollongong have published a world-first proof-of-concept study in the journal Nature Communications, detailing a new tool that can seek out, tag, and destroy toxic proteins linked to motor neurone disease (MND). The breakthrough builds on an idea conceived years ago by the late scientist Justin Yerbury, who died from the disease before the work was completed.
The tool, named Misfold UbL, is a therapeutic designer molecule that targets a mutated protein called SOD1, which is responsible for about 35% of inherited MND cases in Australia. The misfolded SOD1 proteins clump together, damaging and killing motor neurons, leading to muscle weakness, paralysis, and death.
Dr. Christen Chisholm, who led the team after Yerbury's death, described the publication as 'massive on many fronts.' The therapy acts like a 'search and destroy' mechanism, identifying and tagging the misfolded SOD1 proteins so the cell's natural waste-disposal system can degrade them. In tests on mice, the treatment slowed symptom development, protected motor neurons, and preserved muscle connections.
The research was supported by a $1 million grant from the Fight MND charity, awarded in 2020. Dr. Chisholm noted that the achievement is particularly meaningful for the team, as it honors Yerbury's legacy and provides hope for people with MND. The approach may also have applications for other neurodegenerative diseases such as Alzheimer's and Parkinson's.
