Amyloid A (AA) patients who experience disease progression and develop renal failure have not received sufficient benefit from agents that treat inflammation or infection. We are investigating SAA-specific antisense oligonucleotides (ASOs) as a means to specifically suppress serum amyloid A (SAA) production and thereby slow amyloid deposition. Peak SAA levels induced during an acute inflammatory response were 65% lower in ASO-treated mice than in those given saline. To test ASO effect on amyloid deposition, mice were induced to develop amyloid (week 1) and then treated with ASO, 3×per week (weeks 2-5); a second inflammatory stimulus given at the start of week 5. Mice were sacrificed 1 week later and analyzed for amyloid deposition. Spleen, liver, intestine, and heart of all 7 ASO-treated mice contained significantly less amyloid than corresponding organs of 7 saline-treated controls. Other than tiny specks of amyloid, no obvious pathology was seen in mice treated with ASO.
ASJC Scopus subject areas
- Internal Medicine