FoldRx: Unfolding the amyloid mystery
The improper folding of proteins has long been believed to play a role in the pathogenesis of disorders ranging from neurodegenerative diseases to cancer. FoldRx Pharmaceuticals Inc. is developing small molecules designed to inhibit the misfolding and subsequent aggregation of transthyretin (TTR), a protein prevalent in hereditary systemic amyloidosis.
TTR is a tetrameric protein that is primarily synthesized in the liver and is relied on to carry thyroxin and retinal (vitamin A) binding protein in the blood and cerebrospinal fluid. Like most proteins, its proper functioning is based largely on retaining a correct structure. Denaturation stress or even a single amino acid mutation can cause TTR to partially unfold and then refold improperly, increasing its probability of aggregating into amyloidosis...