Transthyretin Cardiac Amyloidosis: Current and Emerging Therapies

In this article, we describe current and newer TTR stabilizers, TTR silencers which include small interfering RNA agents (siRNA), antisense oligonucleotides (ASO) and CRISPR-Cas9 gene editing, and TTR depleters, which investigates the use of monoclonal antibodies to remove amyloid fibril deposits for patients with advanced disease.

Once thought to be a rare and fatal condition, increased recognition, improved non-invasive diagnostic tools, and the explosive development of novel therapies, has transformed the landscape of transthyretin amyloid cardiomyopathy (ATTR-CM). Advances in cardiac imaging with respect to echocardiography, cardiac magnetic resonance imaging (CMR), and radionuclide bone scintigraphy has increased the diagnosis of ATTR-CM over the last twenty years. Ongoing clinical trials are evaluating several novel therapies at several mechanistic targets in the transthyretin (TTR) amyloidogenesis cascade, including the recently published findings from the study of vutrisiran, a siRNA agent.

Our review provides a comprehensive summary of current and emerging therapies for ATTR-CM. While these are promising, disease-modifying treatments, reaching vulnerable populations early in the disease course should be a focus for future studies and interventions.