How does tafamidis work?

• A. It reverses existing fibrils
• B. It increases hepatic synthesis of transthyretin
• C. It slows the formation of new fibrils by binding to an unoccupied T4 binding site
• D. It degrades existing fibrils

Answer: (C)

The key idea is stabilizing the transthyretin tetramer to prevent it from dissociating into misfolding-prone monomers. Tafamidis binds selectively to an unoccupied thyroxine-binding site on the TTR tetramer with high affinity, locking the structure together. By keeping the tetramer intact, it lowers the amount of monomer that can misfold and form new amyloid fibrils, so it slows, rather than reverses, fibril formation. It does not increase hepatic synthesis of transthyretin, nor does it degrade existing fibrils.