{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:12:42Z","timestamp":1791252762288,"version":"4.1.0"},"reference-count":114,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T00:00:00Z","timestamp":1680480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a progressive and increasingly recognized cause of heart failure which is associated with high mortality and morbidity. ATTR-CM is characterized by the misfolding of TTR monomers and their deposition within the myocardium as amyloid fibrils. The standard of care for ATTR-CM consists of TTR-stabilizing ligands, such as tafamidis, which aim at maintaining the native structure of TTR tetramers, thus preventing amyloid aggregation. However, their efficacy in advanced-staged disease and after long-term treatment is still a source of concern, suggesting the existence of other pathogenetic factors. Indeed, pre-formed fibrils present in the tissue can further accelerate amyloid aggregation in a self-propagating process known as \u201camyloid seeding\u201d. The inhibition of amyloidogenesis through TTR stabilizers combined with anti-seeding peptides may represent a novel strategy with additional benefits over current therapies. Finally, the role of stabilizing ligands needs to be reassessed in view of the promising results derived from trials which have evaluated alternative strategies, such as TTR silencers and immunological amyloid disruptors.<\/jats:p>","DOI":"10.3390\/pharmaceutics15041129","type":"journal-article","created":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T01:35:59Z","timestamp":1680572159000},"page":"1129","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Transthyretin Stabilizers and Seeding Inhibitors as Therapies for Amyloid Transthyretin Cardiomyopathy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5962-9143","authenticated-orcid":false,"given":"Paolo","family":"Morfino","sequence":"first","affiliation":[{"name":"Interdisciplinary Center for Health Sciences, Scuola Superiore Sant\u2019Anna, 56127 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9129-9519","authenticated-orcid":false,"given":"Alberto","family":"Aimo","sequence":"additional","affiliation":[{"name":"Interdisciplinary Center for Health Sciences, Scuola Superiore Sant\u2019Anna, 56127 Pisa, Italy"},{"name":"Cardiology Division, Fondazione Toscana Gabriele Monasterio, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7066-6006","authenticated-orcid":false,"given":"Giuseppe","family":"Vergaro","sequence":"additional","affiliation":[{"name":"Interdisciplinary Center for Health Sciences, Scuola Superiore Sant\u2019Anna, 56127 Pisa, Italy"},{"name":"Cardiology Division, Fondazione Toscana Gabriele Monasterio, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9760-8180","authenticated-orcid":false,"given":"Chiara","family":"Sanguinetti","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9285-2328","authenticated-orcid":false,"given":"Vincenzo","family":"Castiglione","sequence":"additional","affiliation":[{"name":"Interdisciplinary Center for Health Sciences, Scuola Superiore Sant\u2019Anna, 56127 Pisa, Italy"},{"name":"Cardiology Division, Fondazione Toscana Gabriele Monasterio, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9496-9370","authenticated-orcid":false,"given":"Maria","family":"Franzini","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0511-2621","authenticated-orcid":false,"given":"Marco Alfonso","family":"Perrone","sequence":"additional","affiliation":[{"name":"Division of Cardiology and CardioLab, Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Emdin","sequence":"additional","affiliation":[{"name":"Interdisciplinary Center for Health Sciences, Scuola Superiore Sant\u2019Anna, 56127 Pisa, Italy"},{"name":"Cardiology Division, Fondazione Toscana Gabriele Monasterio, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2641","DOI":"10.1016\/S0140-6736(15)01274-X","article-title":"Systemic amyloidosis","volume":"387","author":"Wechalekar","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1080\/00015385.2021.1992990","article-title":"Cardiac amyloidosis: A review of the literature","volume":"77","author":"Dulgheru","year":"2022","journal-title":"Acta Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4679","DOI":"10.1093\/eurheartj\/ehac543","article-title":"Restrictive cardiomyopathy: Definition and diagnosis","volume":"43","author":"Rapezzi","year":"2022","journal-title":"Eur. 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