ATTR amyloidosis is a rare disease associated with abnormal folding of the transthyretin (TTR) protein, leading to the deposition of amyloid fibrils in the heart and nervous system. Treatment to date has focused primarily on alleviating symptoms such as heart failure and neuropathy. Currently available disease-modifying therapies include TTR stabilizers (tafamidis, acoramidis), which prevent TTR tetramer dissociation, and gene silencers (siRNA and ASO), which reduce TTR production and slow the progression of polyneuropathy. Modern experimental strategies, including CRISPR-Cas9 gene editing and anti-ATTR monoclonal antibodies, offer the potential for one-time treatment and removal of existing amyloid deposits. The choice of therapy should be tailored to the patient's phenotype, disease stage, and clinical capabilities, and ongoing research will better determine the long-term efficacy and safety of new drugs. The aim of this paper is to present contemporary therapeutic strategies in the treatment of transthyretin amyloidosis (ATTR), with particular emphasis on disease-modifying drugs such as TTR stabilizers, gene silencers, CRISPR-Cas9 gene editing therapies, and anti-ATTR monoclonal antibodies. The paper aims to evaluate the efficacy and safety of available therapies, discuss their clinical indications depending on the patient's phenotype (polyneuropathy, cardiomyopathy), and present directions for the development of new therapeutic strategies based on current clinical trials.
Pietruszewska et al. (Wed,) studied this question.