TTR Amyloidosis

Transthyretin (previously called prealbumin),a protein made by the liver, is present in blood and in the brain and is a carrier of thyroxin and retinol (vitamin A) binding protein. Transthyretin (TTR) normally circulates in the blood as four protein units linked together (also called a tetramer). However a single amino acid abnormality or aging can lead to the tetramer coming apart, with the individual protein units folding abnormally, resulting in the accumulation of these misfolded TTR protein units as amyloid, leading to TTR associated amyloidosis (ATTR). There are over 100 mutations in transthyretin, of which over 80 are associated with systemic amyloidosis. This disease in inherited as an autosomal dominant disease, which means that only one copy of the abnormal gene is necessary.

TTR amyloid is deposited primarily along the peripheral nerves and in the heart, as well as in the gastrointestinal tract, vitreous (eye) and elsewhere. The primary site of TTR amyloid deposition determines the phenotypic, or clinical presentation of the disease.

FoldRx Pharmaceuticals has drugs that stabilize TTR and prevent its misfolding. Tafamidis (Fx-1006A) is a novel, selective, potent TTR stabilizer compound and was recently evaluated in a Phase II/III multi-center, international study in patients with V30M ATTR-PN.