La cardiomiopatia amiloidotica correlata alla transtiretina: Alla ricerca del trattamento eziologico

Transthyretin (TTR)-related amyloidosis is a disease caused by the deposition of insoluble fibrils deriving from the misfolding of TTR, a protein mainly produced by the liver. In the hereditary form of the disease (ATTRm), protein misfolding is secondary to a mutation in the TTR gene. ATTRm can manifest with different phenotypes: mainly neurological, mainly cardiac, or mixed. In the senile form of the disease (wild-type TTR or SSA), the deposition of non-mutated TTR occurs and, clinically, cardiomyopathy is predominant. Cardiac amyloidosis is still an underdiagnosed disease and clinical heterogeneity makes the diagnosis challenging. Until recently, no specific pharmacological treatment was available, liver transplantation being the only therapeutic option aimed at slowing disease progression in ATTRm and treatment was based on symptom relief. This review focuses on the emerging pharmacological treatments for TTR-related amyloidosis targeting different steps of the amyloidogenic process (blocking hepatic TTR synthesis, TTR tetramer stabilization and promotion of TTR amyloid fibril clearance). © 2014 Il Pensiero Scientifico Editore.