Amyloidosis is the extracellular accumulation of fibrils made up of insoluble, misfolded proteins, which can negatively impact tissue structures, such as the heart. One such mutant and wild-type protein is transthyretin (TTR). It is linked to two distinct cardiac amyloidosis: hereditary TTR-related amyloidosis and the nonhereditary systemic senile amyloidosis [1]. TTR amyloid cardiomyopathy results when the TTR tetramers get destabilized and deposited in the heart. Acoramidis (AG10) can serve as a potential first-line drug by selectively stabilizing TTR [2].
AG10, a selective TTR stabilizer, significantly reduced overall results and all-cause mortality outcomes in patients with TTR amyloid cardiomyopathy. Additionally, serum plasma concentrations of pro-brain natriuretic peptide were significantly reduced with the drug given a dose of 200 mg twice daily [3]. Another recent study by Gillmore et al. [2] highlighted the unprecedented safety profile and tolerability (53.7%) of AG10 compared to placebo (35.9%), favoring acoramidis in reducing heart failure. The drug also successfully minimized plasma pro-brain natriuretic peptide levels (23.3%) relative to the placebo group (7%). Furthermore, the incidence of adverse effects was lowered in the treatment group. Despite its name, TTR’s contribution to thyroxine or retinol transport does not entirely affect their homeostasis. Instead, it has shown beneficial effects on cardiovascular-related hospitalization. Another recent novel study has disclosed that the patients suffering from wild-type TTR cardiac amyloidosis when treated with AG10 revealed marked elevation of TTR levels in the serum (29% and 34% at the doses of 400 mg and 800 mg, respectively) compared to the patients who were treated with other stabilizers [4].
TTR amyloid cardiomyopathy is a highly debilitating disease with a mean survival time of 26–70 months after diagnosis, having a mortality rate of 13% due to heart failure with preserved ejection fraction [5]. AG10 has proved to be a spark of hope for tackling this disease, improving overall health outcomes, and halting the disease’s progression. Further studies on larger population sizes are required to determine the long-term treatment benefits and net effects fully.
Conflict of Interest Statement
The authors have no conflicts of interest to declare.
Funding Sources
This study was not supported by any sponsor or funder.
Author Contributions
Author M.S.B.F. contributed to conceptualization, validation, resources, writing – original draft, review, and editing, supervision, and project administration. Author G.I. contributed to writing – original draft.
