Emerging therapies and translational tools for drug development in systemic amyloidosis: insights from the International Society of Amyloidosis Scientific Workshop.

Abstract

Amyloidosis is caused by deposition of misfolded proteins as amyloid fibrils in multiple organs. Over the past decade, disease-modifying therapies have markedly improved outcomes in both amyloid light-chain (AL) amyloidosis and amyloid transthyretin (ATTR) amyloidosis. Progress in AL amyloidosis has been driven by advances in plasma cell-directed therapies that suppress production of the precursor light chains. In ATTR amyloidosis, therapies target distinct phases of the amyloid cascade. The efficacy of multiple therapies that block production or misfolding of transthyretin has led to regulatory approvals. By contrast, limited efficacy has been observed to date with amyloid-targeting antibodies designed to clear existing amyloid deposits. This perspective article presents insights from experts representing the International Society of Amyloidosis reviewing current and emerging treatments for AL and ATTR amyloidosis, discussed at the 2025 Scientific Workshop. Recent advances in research tools (animal and induced pluripotent stem cell (iPSC)-based models) are discussed as valuable approaches for disease modeling and preclinical evaluation of novel therapies. Lastly, the growing role of artificial intelligence in accelerating drug discovery in systemic amyloidosis is examined. Alongside recent successes and ongoing progress, there are key unmet needs and limitations that must be overcome to further improve patient outcomes.