{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T08:38:48Z","timestamp":1774946328432,"version":"3.50.1"},"reference-count":10,"publisher":"IMR Press","issue":"3","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rev. Cardiovasc. Med."],"abstract":"<jats:p>Background: Transthyretin cardiac amyloidosis (ATTR-CA) results from the extracellular deposition of misfolded transthyretin (mis-TTR) and promotes progressive cardiac dysfunction. Current therapies, such as stabilizers and silencers, reduce further fibril accumulation but fail to clear existing deposits. Monoclonal antibodies (mAbs) targeting mis-TTR have emerged as promising disease-modifying agents, supported by recent observations of circulating anti-TTR antibodies in patients who exhibited spontaneous clinical improvement. Methods: This study aimed to purify natural anti-TTR antibodies from two ATTR-CA patients and compare the respective binding properties to those of a previously described therapeutic anti-TTR mAb fragment (Ab-A F(ab')2). Statistical significance was determined using Student's t-test. Results: Both natural antibodies and the Ab-A F(ab')2 demonstrated high-affinity binding to misfolded TTR (n = 3), while the competition assays revealed dose-dependent inhibition, indicating shared epitope recognition. Conclusions: These findings provide translational evidence that therapeutic anti-TTR mAbs may mimic naturally protective antibodies, suggesting that these antibodies could promote amyloid clearance and deliver true disease-modifying benefits in ATTR-CA.<\/jats:p>","DOI":"10.31083\/rcm48514","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T07:28:46Z","timestamp":1774942126000},"source":"Crossref","is-referenced-by-count":0,"title":["Shared Binding Properties Between a Therapeutic Antibody and Anti-Transthyretin Antibodies From Transthyretin Cardiac Amyloidosis Patients: Translational Implications for Future Clinical Trials"],"prefix":"10.31083","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1811-1118","authenticated-orcid":true,"given":"Jacob","family":"George","sequence":"first","affiliation":[{"name":"Cognyxx Pharmaceuticals, 6901648 Tel Aviv, Israel"},{"name":"Heart Center, Kaplan Medical Center, 76100 Rehovot, Israel"},{"name":"Hebrew University, 9190501 Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Benaim","sequence":"additional","affiliation":[{"name":"Cognyxx Pharmaceuticals, 6901648 Tel Aviv, Israel"},{"name":"Heart Center, Kaplan Medical Center, 76100 Rehovot, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Fassler","sequence":"additional","affiliation":[{"name":"Cognyxx Pharmaceuticals, 6901648 Tel Aviv, Israel"},{"name":"Heart Center, Kaplan Medical Center, 76100 Rehovot, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Ruberg FL, Grogan M, Hanna M, Kelly JW, Maurer MS. Transthyretin Amyloid Cardiomyopathy: JACC State-of-the-Art Review. Journal of the American College of Cardiology. 2019; 73: 2872\u20132891.","DOI":"10.1016\/j.jacc.2019.04.003"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. New England Journal of Medicine. 2018; 379: 1007\u20131016.","DOI":"10.1056\/NEJMoa1805689"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Gillmore JD, Judge DP, Cappelli F, Fontana M, Garcia-Pavia P, Gibbs S, et al. Efficacy and safety of acoramidis in transthyretin amyloid cardiomyopathy. New England Journal of Medicine. 2024; 390: 132\u2013142.","DOI":"10.1056\/NEJMoa2305434"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Fontana M, Berk JL, Gillmore JD, Witteles RM, Grogan M, Drachman B, et al. Vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy. New England Journal of Medicine. 2025; 392: 33\u201344.","DOI":"10.1056\/NEJMoa2409134"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Masri A, Bhattacharya P, Medoff B, Ejaz AU, Elman MR, Chandrashekar P, et al. A Multicenter Study of Contemporary Long-Term Tafamidis Outcomes in Transthyretin Amyloid Cardiomyopathy. JACC. CardioOncology. 2025; 7: 282\u2013293.","DOI":"10.1016\/j.jaccao.2024.12.005"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Suhr OB, Grogan M, Silva AMD, Karam C, Garcia-Pavia P, Drachman B, et al. PRX004 in variant amyloid transthyretin (ATTRv) amyloidosis: results of a phase 1, open-label, dose-escalation study. Amyloid: the International Journal of Experimental and Clinical Investigation: the Official Journal of the International Society of Amyloidosis. 2025; 32: 14\u201321.","DOI":"10.1080\/13506129.2024.2420809"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Garcia-Pavia P, Aus dem Siepen F, Donal E, Lairez O, van der Meer P, Kristen AV, et al. Phase 1 Trial of Antibody NI006 for Depletion of Cardiac Transthyretin Amyloid. The New England Journal of Medicine. 2023; 389: 239\u2013250.","DOI":"10.1056\/NEJMoa2303765"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"George J, Rappaport M, Shimoni S, Goland S, Voldarsky I, Fabricant Y, et al. A novel monoclonal antibody targeting aggregated transthyretin facilitates its removal and functional recovery in an experimental model. European Heart Journal. 2020; 41: 1260\u20131270.","DOI":"10.1093\/eurheartj\/ehz695"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Fontana M, Gilbertson J, Verona G, Riefolo M, Slamova I, Leone O, et al. Antibody-Associated Reversal of ATTR Amyloidosis-Related Cardiomyopathy. The New England Journal of Medicine. 2023; 388: 2199\u20132201.","DOI":"10.1056\/NEJMc2304584"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Tuvali O, Fassler M, Goland S, Benaim C, Shimoni S, George J. A functional role for spontaneously occurring natural anti-transthyretin antibodies from patients with transthyretin cardiac amyloidosis. European Journal of Heart Failure. 2024.  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