Current evidence suggests that monoclonal antibodies (mAb) directed against plasma cell clones could be a promising strategy to treat cardiac amyloidosis in transthyretin amyloidosis (ATTR), of which hereditary transthyretin amyloidosis (hATTR) is a form, and immunoglobulin light-chain amyloidosis, as recently reviewed by experts from Italy.

“A therapeutic strategy based on monoclonal antibodies capable of selectively binding amyloid deposits and inducing their removal has recently been tested in various clinical trials, with promising results, and could represent a key treatment for CA [cardiac amyloidosis] in the near future,” the experts wrote in European Heart Journal Supplements.

Three mAbs were considered for clinical evaluation in ATTR. One of them, PRX004, is a humanized mAb specifically designed to treat hATTR. However, the phase 1 study (NCT03336580) evaluating the safety of PRX004 was terminated early due to the COVID-19 pandemic even though the study’s authors reported an improved global longitudinal strain among the 7 patients with available cardiac involvement. Moreover, there were no treatment-related serious adverse events reported.

Additional mAbs for ATTR included NI301A and Ab-A. NI301A, a human mAb, is currently being evaluated in a phase 1 study (NCT04360434) in patients with ATTR-related cardiomyopathy. Mechanistically, it has been shown that NI301A binds to the linear epitope WEPFA, which is only accessible on the misfolded transthyretin protein and ATTR deposits. Therefore, NI301A induces phagocytosis of ATTR aggregates by human macrophages and promotes the removal of fibrils.

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Ab-A is a human immunoglobulin G1 mAb that binds with high affinity to aggregated TTR, thus leading to significant removal of ATTR aggregates through phagocytosis. Studies exploring Ab-A were conducted in a murine model of wild-type ATTR and in human heart tissue samples with wild-type ATTR amyloidosis.

Recently, a novel strategy has arisen from the development of pan-amyloid removal therapeutics. This strategy uses molecules that can selectively bind to amyloid deposits in all types of amyloidosis and at all stages of the disease, thereby showing a wide potential of application.

Overall, these anti-amyloid mAb-based therapeutics show potential as complementary and synergistic approaches to current therapies for cardiac amyloidosis, which can only block the deposition of additional amyloid, rather than remove pre-existing deposits.

“Future studies evaluating combination therapies with drugs that reduce circulating levels of the amylogenic precursor and others that accelerate the amyloid removal from tissues are highly warranted,” the experts said.


Emdin M, Morfino P, Crosta L, Aimo A, Vergaro G, Castiglione V. Monoclonal antibodies and amyloid removal as a therapeutic strategy for cardiac amyloidosis. Eur Hear J Suppl. 2023;25(Supplement_B):B79-B84. doi:10.1093/eurheartjsupp/suad079