A library of ATTR amyloidosis patient-specific induced pluripotent stem cells for disease modelling and in vitro testing of novel therapeutics

Abstract

Hereditary transthyretin amyloidosis (ATTR amyloidosis) is an autosomal dominant protein-folding disorder caused by over 100 distinct mutations in the transthyretin (TTR) gene. In ATTR amyloidosis, protein secreted from the liver aggregates and forms amyloid fibrils in downstream target organs, chiefly the heart and peripheral nervous system. Few animal models of ATTR amyloidosis exist and none recapitulate the multisystem complexity and clinical variability associated with disease pathogenesis in patients. Induced pluripotent stem cells (iPSCs) stand to revolutionize the way we study human development, model disease, and perhaps treat patients afflicted with highly variable multisystem diseases such as ATTR amyloidosis. Here, we fully characterize six representative iPSC lines from a library of previously reprogrammed iPSC lines and reprogrammable blood samples derived from ATTR amyloidosis patients. This unique resource, described herein, can be harnessed to study diverse disorder.

Keywords:

• ATTR
• hereditary ATTR amyloidosis
• pluripotent stem cells
• disease modelling
• drug discovery

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This work was funded by National Institute of Diabetes and Digestive and Kidney Diseases [grant number: 1R01DK102635–01], National Institutes of Health [grant numbers: R01AG031804, 2R56AG031804–06A1] and also by the Boston University School of Medicine Young Family Amyloid Research Fund.