By exploring the biophysics of proteins with disease-associated mutations, a UCSF group has developed a way to screen for drugs that rescue the activity of non-enzymatic targets, and proved its value with molecular chaperones. After finding a compound that clears up cataracts, the team formed ViewPoint Therapeutics Inc. to commercialize its approach under the wing of JLABS, Johnson & Johnson's network of life sciences incubators.
The cataract study, published last week in Science, is the first application of what ViewPoint hopes will be a widely applicable strategy for targeting disease-associated mutations whose phenotypic effects are unclear. Leah Makley, CSO of ViewPoint and first author on the study, thinks the broad biophysical approach will open the doors to targets about which there is little information.
"In the post-genomic era, the field has identified new classes of protein targets that have been implicated in disease through genetic screens, but we have a poor understanding of the structure and function of many of these new targets," she said.
Makley began the study by seeking an approach to target non-enzymatic molecules like molecular chaperones, whose lack of catalytic readout had made high throughput screening strategies elusive. "I was particularly interested in looking at protein targets that were labeled undruggable," she said.
The study began in 2011 at the University of Michigan under principal investigator