Marcus Vinícius Simões et al. Fábio Fernandes André Dabarian Flavio Henrique Valicelli Claudio Tinoco Mesquita
Abstract
Amyloidosis is caused by the extracellular deposition of insoluble protein arrangements, formed from structural changes in different precursor proteins. The prominent clinical and epidemiological relevance of transthyretin amyloid cardiomyopathy (ATTR-CM), whose increased incidence is associated with the aging of the global population, given its high prevalence in the elderly population, has motivated the intensification of the search for specific therapeutic targets capable of altering the natural course of the disease. The past few years have been especially prolific with the emergence of significant new therapies for ATTR-CM, with important trials demonstrating positive results and changing the natural history of an inexorable and deadly disease. Up to now, the available drugs mainly promote stabilization of disease progression in patients with no advanced heart disease but grant no reversal of the structural cardiac disease in most cases. The transthyretin (TTR)-depleters based on monoclonal antibodies directed against the deposited amyloid fibers hold promise to fulfill these expectations. The DepleTTR-CM will test the safety and efficacy of a monoclonal antibody directed against TTR fibrils deposited in the myocardium of patients with ATTR-CM. This will be the first multicenter randomized controlled trial to test this new class of anti-amyloid treatment, the “amyloid fibril depleters”. This is a strategy designed to revert the amyloid accumulation in the cardiac interstitium, which is expected to translate into relevant clinical benefits, with the potential to close a gap in the ATTR-CM treatment strategies, mainly in patients with more severe disease.