News Finding: In ATTR, protein secreted from the liver aggregates and forms fibrils in target organs, chiefly the heart and peripheral nervous system, highlighting the need for a model capable of duplicating the multisystem complexity of this clinically variable disease.
Paper Finding: In ATTR, protein secreted from the liver aggregates and forms fibrils in target organs, chiefly the heart and peripheral nervous system, highlighting the need for a model capable of recapitulating the multisystem complexity of this clinically variable disease.
News Context: The findings, which are reported in Stem Cell Reports, may lead to new treatments for genetic diseases such as familial amyloidosis. In ATTR, protein secreted from the liver aggregates and forms fibrils in target organs, chiefly the heart and peripheral nervous system, highlighting the need for a model capable of duplicating the multisystem complexity of this clinically variable disease. According to researchers using iPSC technology, cell lines can be established that are genetically identical to the individual from whom they are derived, allowing for disease modeling and development of novel therapeutics in the personalized genetic context of the patient from which they are made.
Paper Context: In ATTR, protein secreted from the liver aggregates and forms fibrils in target organs, chiefly the heart and peripheral nervous system, highlighting the need for a model capable of recapitulating the multisystem complexity of this clinically variable disease. We demonstrate that iPSC-derived neuronal and cardiac cells display oxidative stress and an increased level of cell death when exposed to mutant TTR produced by the patient-matched iPSC-derived hepatocytes, recapitulating essential aspects of the disease in vitro. Furthermore, small molecule stabilizers of TTR show efficacy in this model, validating this iPSC-based, patient-specific in vitro system as a platform for testing therapeutic strategies.