Abstract
Transthyretin is a protein synthetized mostly by the liver, which normaly forms tetramers. As a result of gene mutations or as an ageing related phenomenon, transthyretin molecules may disfold (loose their normal space conformation) and deposit in the heart or in other organs as amyloid.
Cardiac involvement in transthyretin related cardiomyopathy manifests typically as left ventricular pseudohypertrophy and/or heart failure with preserved ejection fraction. ATTR cardiomyopathy is relatively rare disease with bad prognosis.
Untill recently no effective specific pharmacological tratment did exist, just symptomatic treatment, mostly by diuretics for dyspnoe relief. The therapeutic options now include several new drugs targeting amyloidogenesis at different steps and by different mechanisms.
Following the positive results of ATTR ACT study, tafamidis was recently registered for the treatment of ATTR cardiopmyopathy. This drug stabilizes the transthyretin tetramers.
There are also transthyretin synthesis inhibiting drugs patisiran and inotersen in an advanced phase of clinical research.