Abstract 464: Novel Anti-Medin Antibodies Detect Medin Amyloid Deposits in the Aorta of Patients with Thoracic Aneurysms or Marfan Syndrome

Introduction: Medin, a 50 aa cleavage fragment of MFG-E8/ lactadherin appears to self assemble into fibrils and form the amyloid deposits seen in patients with aortic aneurysms. While the pathogenic nature of these aggregates is not fully understood, it appears medin may perturb smooth muscle cell function and thereby weaken the integrity of the aorta wall. One approach to treat aortic aneurysms may be to sequester medin and thereby block aggregation or remove the amyloid deposits from the aorta using a monoclonal antibody. Methods: Mice were immunized with a c-terminal peptide or full-length human medin, hybridomas cloned and antibodies screened for activity using ELISA, Western blot, Biacore and immunocytochemistry. Results: Initial ELISA studies revealed that antibodies raised against full-length 50 aa medin (e.g. 6B3) bind both medin peptide and MFG-E8, while antibodies raised against a c-terminal peptide (e.g. 18G1) appeared to be medin specific. Subsequent studies confirmed these observations and re...