TTR Amyloidosis
ALN-TTR: TTR Amyloidosis
We are developing ALN-TTR, a systemically delivered RNAi therapeutic that targets the transthyretin (TTR) gene, to treat TTR-mediated amyloidosis (ATTR).
ATTR is caused by mutations in the TTR gene, which is expressed predominantly in the liver, and results in the accumulation of pathogenic deposits of mutant and wild-type TTR protein in multiple extra-hepatic tissues, including the peripheral nervous system, heart, and the gastrointestinal tract.
Pre-clinical studies in a mouse transgenic model have shown that treatment with ALN-TTR01 results in both prevention and regression of pathogenic TTR deposits in peripheral tissues including dorsal root ganglia, sciatic nerve, stomach, and intestines. Further, ALN-TTR01 administration in non-human primates was found to result in dose-dependent and durable, yet reversible silencing of the TTR gene and serum levels of TTR.For most patients with TTR amyloidosis, liver transplantation is the only treatment option. These data suggest that treatment of TTR amyloidosis with an RNAi therapeutic may represent a promising alternative medical strategy.
In July 2010, we initiated dosing in a Phase I human clinical study with ALN-TTR01. The study is aimed at evaluating the safety and tolerability of ALN-TTR01 in patients with ATTR, and is also designed to provide preliminary data on human proof of concept based on measurements of TTR serum levels.
ALN-TTR01 employs a first generation lipid nanoparticle formulation developed in collaboration with Tekmira Pharmaceuticals Corporation. In parallel, we are also advancing ALN-TTR02 utilizing second-generation lipid nanoparticles.
ALN-TTR Clinical Timeline

