Eprodisate for the Treatment of Renal Disease in AA Amyloidosis

• Published in: The New England journal of medicine Vol. 356; no. 23; pp. 2349 - 2360
• Main Authors: Dember, Laura M, Hawkins, Philip N, Hazenberg, Bouke P.C, Gorevic, Peter D, Merlini, Giampaolo, Butrimiene, Irena, Livneh, Avi, Lesnyak, Olga, Puéchal, Xavier, Lachmann, Helen J, Obici, Laura, Balshaw, Robert, Garceau, Denis, Hauck, Wendy, Skinner, Martha
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 07.06.2007
• Subjects: Amyloidosis - drug therapy; Amyloidosis - etiology; Amyloidosis - mortality; Arthritis, Rheumatoid - complications; Creatinine - blood; Disease Progression; Double-Blind Method; Familial Mediterranean Fever - complications; Female; Glycosaminoglycans - antagonists & inhibitors; Humans; Kaplan-Meier Estimate; Kidney Diseases - drug therapy; Kidney Diseases - etiology; Kidney Diseases - mortality; Kidney Failure, Chronic - prevention & control; Male; Microscopy; Middle Aged; Molecular weight; Propane - adverse effects; Propane - analogs & derivatives; Propane - therapeutic use; Proportional Hazards Models; Proteins; Proteinuria; Rodents; Serum Amyloid A Protein - drug effects; Sulfonic Acids - adverse effects; Sulfonic Acids - therapeutic use
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa065644

Amyloid A (AA) amyloidosis, a complication of chronic inflammatory conditions, develops when proteolytic fragments of serum amyloid A protein are deposited in tissues as amyloid fibrils. This placebo-controlled trial investigated the effect of eprodisate, a small molecule that inhibits amyloid fibril polymerization and tissue deposition in patients with renal AA amyloidosis. As compared with placebo, the drug slowed a decline in renal function. Eprodisate is a member of a new class of compounds that interfere with interactions between amyloidogenic proteins and glycosaminoglycans. This trial investigated the effect of eprodisate, a small molecule that inhibits amyloid fibril polymerization and tissue deposition in patients with renal AA amyloidosis. As compared with placebo, the drug slowed a decline in renal function. The amyloidoses constitute a group of diseases in which proteins are deposited extracellularly in the tissues as insoluble fibrils, causing progressive organ dysfunction and death. 1 Amyloid A (AA) amyloidosis, also referred to as secondary amyloidosis, is a rare but serious complication of chronic inflammatory diseases and chronic infections. The amyloidogenic protein in AA amyloidosis is a proteolytic fragment of serum amyloid A protein (SAA), an acute-phase reactant produced by the liver. The kidney is the organ most frequently affected in AA amyloidosis. 2 Ongoing deposition of amyloid in the kidney results in proteinuria and progressive loss of renal function. The gastrointestinal . . .