Evaluierung therapeutischer Oligonukleotide zur Therapie der familiären Amyloidose in einem Stammzell-abgeleiteten Zellmodell

Einleitung: Familial amyloid polyneuropathy (FAP) is caused by mutations of the transthyretin (TTR) gene. TTR is secreted into the blood, predominantly by the liver. The tetramer can undergo dissociation resulting in extracellular tissue deposition of TTR, followed by dysfunctions in target tissues. The effects of an antisense oligonucleotide (ASO; IONIS-TTRRx) and small interfering RNA (siRNA; ALN-TTR-02) on TTR synthesis are currently being evaluated in phase II/III clinical trials in patients with FAP. Primary hepatocytes from FAP patients are rarely available for molecular analysis and commercial tissue culture cells do not have the genetic background of individual patients.