Stabilizers, Silencers, and Depleters: Exploring New Frontiers Treating ATTR-CM

Amyloidosis is a disease of protein misfolding. Proteins misfold, aggregate, and deposit into tissues as insoluble amyloid fibrils. These amyloid fibrils cause mechanical tissue disruption and local oxidative stress, ultimately resulting in organ dysfunction. Transthyretin (TTR), also known as prealbumin, is produced by the liver and serves as a carrier protein for thyroxine and retinol binding protein. Under normal circumstances, TTR circulates as a tetramer. However, in TTR amyloidosis, TTR tetramers dissociate into monomers, which are prone to misfolding into amyloid fibrils and inflicting damage to the body’s tissues and organ systems. When TTR amyloid affects the heart, this is called transthyretin amyloid cardiomyopathy (ATTR-CM), or transthyretin cardiac amyloidosis.^1-3