Shared Binding Properties Between a Therapeutic Antibody and Anti-Transthyretin Antibodies From Transthyretin Cardiac Amyloidosis Patients: Translational Implications for Future Clinical Trials
Reviews in Cardiovascular Medicine 2026 Mar 9;27(3):48514. Jacob George, Clara Benaim, Michael Fassler DOI: https://doi.org/10.31083/RCM48514
Abstract:
"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."
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