New Drug Target Blocks Protein Accumulation in ALS, Alzheimer’s
15 January 2016
A breakdown in protein metabolism, leading to the accumulation of misfolded proteins, is a hallmark of ALS, Alzheimer’s, and other neurodegenerative diseases. Two recent papers published by Project ALS Research Advisor Alfred Goldberg (Harvard) and collaborators in Karen Duff’s lab (Columbia) show that by enhancing the cell’s “ubiquitin-proteasome pathway”—essentially, its protein waste removal system—we can clear toxic proteins and restore function in these fatal brain diseases.
These studies, published in Nature Medicine (Jan ’16) and Proceedings of the National Academy of Sciences (Dec ’15), showed that Rolipram, a brain-penetrant drug originally developed to treat depression, boosts the activity of the ubiquitin-proteasome pathway, diminishing protein accumulation in stem cell models of ALS and improving cognitive function in an Alzheimer’s mouse model.
Now, Goldberg and fellow Project ALS Research Advisor Robert Brown (UMass) are testing this discovery in ALS mouse models, with the goal of validating these findings and moving into human clinical trials as quickly as possible.