In the mid-1990s, as the mad-cow-disease scare spread across Europe, scientists were beginning to accept a controversial idea: perhaps this contagious brain-wasting ailment was caused not by a virus or bacterium but by a protein already found in the body. Subtle changes in the shape of the normally benign protein could be enough to transform it into a deadly agent that turned the brains of cows and a few unlucky beef eaters into mush. Stranger still, researchers were beginning to find that other misshapen proteins were at the root of common ailments like Parkinson's disease, Alzheimer's disease, diabetes, and even cancer.

It was around this time that two of the leading scientists studying shape-shifting proteins -- Susan Lindquist, then at the University of Chicago, and Jeffery Kelly of the Scripps Research Institute -- began discussing the potential of drugs that prevent proteins from getting bent out of shape and unleashing their toxic effects. "I would say that within our first two conversations, we talked about starting up a company," says Lindquist, who is now at MIT. And so was born the idea for FoldRx Pharmaceuticals. But the Cambridge, MA–based company didn't actually get off the ground until December 2003, shortly before Lindquist left her post as director of MIT's Whitehead Institute for Biomedical Research. Despite that lag, FoldRx is still one of only a few startups developing drugs that target misshapen -- or misfolded, as researchers typically call them -- proteins.