administer drugs prophylactically,” says Jeff Kelly, senior author of the study appearing in the issue of Science. “There’s reason to believe that they could be useful after the disease manifests itself clinically. I’m really optimistic that this will be useful no matter how you do it – as long as you do it, as long as people get treated.”
Amyloid diseases, which include multiple myeloma, rheumatoid arthritis, Crohn’s disease, ulcerative colitis, transthyretin, cutaneous, Alzheimer’s, Parkinson’s, cystic fibrosis and mad cow disease, result when misfolded proteins amass to form amyloids, which are plaque-like structures that crowd different organs in the body.
Much research has focused on dealing with the amyloids once they are formed. The authors of this study intervened a step earlier.
Under normal conditions, proteins fold themselves into three-dimensional structures that then perform work much like screws and bolts, says Marc Gillespie, a professor of pharmaceutical sciences at St. John’s University in Queens, N.Y. How exactly proteins acquire their specific shape, has been a bit of a mystery. “It’s the equivalent of taking a string of pearls and getting a steering wheel out of it,” Gillespie says.
The authors of this study looked at a case of a protein gone awry: transthyretin amyloid diseases, which involve misfolding of the protein transthyretin (TTR). TTR is secreted by the liver into the bloodstream, where it acts as a transporter for thyroid hormone and vitamin A.
Normal TTR is composed of four identical copies of the protein that bind to each other. Certain genetic defects, however, cause this structure (called a tetramer) to come apart easily, giving the parts the chance to change shape, misfold, and come back together into the dreaded amyloid fibrils.
The researchers designed small