A Step Forward in Solving Amyloidosis

This editorial reviews advances in understanding and treating cardiac amyloidosis, particularly transthyretin (ATTR) amyloidosis and evaluates the findings from the APOLLO-B trial. ATTR cardiomyopathy stems from misfolding of transthyretin protein, driven either by genetic variants (variant ATTR) or age-related stability loss (wild-type ATTR). Disease progression involves tetramer dissociation, proteolysis, fibril formation, and organ damage. Patisiran, a liver-targeted siRNA that silences transthyretin production, showed rapid serum transthyretin reduction and preserved cardiac function (6-minute walk test, KCCQ score) in the trial, although no significant differences in cardiovascular events were noted at 12 months. The trial affirms that reducing amyloidogenic precursors yields clinical benefit, mirroring AL amyloidosis findings. The editorial stresses improved diagnostic methods (e.g. bone scintigraphy), evolving surrogate endpoints (NT-proBNP, CMR, PET), and combination therapy potential (e.g. patisiran + tafamidis), while highlighting access challenges. Future strategies include gene editing and monoclonal antibodies like NI006.

This editorial reviews advances in understanding and treating cardiac amyloidosis, particularly transthyretin (ATTR) amyloidosis and evaluates the findings from the APOLLO-B trial. ATTR cardiomyopathy stems from misfolding of transthyretin protein, driven either by genetic variants (variant ATTR) or age-related stability loss (wild-type ATTR). Disease progression involves tetramer dissociation, proteolysis, fibril formation, and organ damage. Patisiran, a liver-targeted siRNA that silences transthyretin production, showed rapid serum transthyretin reduction and preserved cardiac function (6-minute walk test, KCCQ score) in the trial, although no significant differences in cardiovascular events were noted at 12 months. The trial affirms that reducing amyloidogenic precursors yields clinical benefit, mirroring AL amyloidosis findings. The editorial stresses improved diagnostic methods (e.g. bone scintigraphy), evolving surrogate endpoints (NT-proBNP, CMR, PET), and combination therapy potential (e.g. patisiran + tafamidis), while highlighting access challenges. Future strategies include gene editing and monoclonal antibodies like NI006.